Host-Directed therapeutics for tuberculosis: Can we harness the host?

Microbiology and Molecular Biology Reviews

Volumn 77, Issue 4, 2013, Pages 608-627

  Hawn, Thomas R ^a   Matheson, Alastair I ^b   Maley, Stephen N ^b   Vandal, Omar ^c  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c BILL AND MELINDA GATES FOUNDATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 5 NITROBENZANILIDE; ACETYLSALICYLIC ACID; ALISPORIVIR; BERBERINE; BR 49653; CIGLITAZONE; CILOSTAZOL; COLECALCIFEROL; DESIPRAMINE; ERGOCALCIFEROL; ETANERCEPT; ISONIAZID; MEPENZOLATE; NETOGLITAZONE; NITAZOXANIDE; OXIDOREDUCTASE; PENTOXIFYLLINE; PERFLUORONONANOIC ACID; PREDNISOLONE; PROTEIN KINASE R; PYRAZINAMIDE; RAPAMYCIN; RECOMBINANT GAMMA INTERFERON; RHODANINE; RIVOGLITAZONE; SILDENAFIL; THALIDOMIDE; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG; VITAMIN D;

ANTIBIOTIC THERAPY; AUTOPHAGY; BACTERIAL LOAD; CELL DEATH; DRUG DOSE COMPARISON; HOMEOSTASIS; HOST PATHOGEN INTERACTION; IMMUNE RESPONSE; LIPID METABOLISM; MACROPHAGE; MACROPHAGE FUNCTION; MENINGITIS; MYCOBACTERIUM TUBERCULOSIS; PHAGOSOME; REVIEW; TREATMENT DURATION; TUBERCULOSIS;

ANIMALS; ANTI-BACTERIAL AGENTS; HOST-PATHOGEN INTERACTIONS; HUMANS; MYCOBACTERIUM TUBERCULOSIS; TUBERCULOSIS;

EID: 84890521233     PISSN: 10922172     EISSN: 10985557     Source Type: Journal    
DOI: 10.1128/MMBR.00032-13     Document Type: Review

References (202)

1. Berrington WR, Hawn TR. 2007. Mycobacterium tuberculosis, macrophages, and the innate immune response: does common variation matter? Immunological Rev. 219:167-186
2. Ishikawa E, Ishikawa T, Morita YS, Toyonaga K, Yamada H, Takeuchi O, Kinoshita T, Akira S, Yoshikai Y, Yamasaki S. 2009. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J. Exp. Med. 206:2879-2888
3. Liu PT, Modlin RL. 2008. Human macrophage host defense against Mycobacterium tuberculosis. Curr. Opin. Immunol. 20:371-376
4. Manzanillo PS, Shiloh MU, Portnoy DA, Cox JS. 2012. Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages. Cell Host Microbe 11:469-480
5. Russell DG. 2011. Mycobacterium tuberculosis and the intimate discourse of a chronic infection. Immunol. Rev. 240:252-268
6. Russell DG, Barry CE, III, Flynn JL. 2010. Tuberculosis: what we don't know can, and does, hurt us. Science 328:852-856
7. Tailleux L, Pham-Thi N, Bergeron-Lafaurie A, Herrmann JL, Charles P, Schwartz O, Scheinmann P, Lagrange PH, de Blic J, Tazi A, Gicquel B, Neyrolles O. 2005. DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis. PLoS Med. 2:e381. doi:10.1371/journal.pmed.0020381
8. Tailleux L, Schwartz O, Herrmann JL, Pivert E, Jackson M, Amara A, Legres L, Dreher D, Nicod LP, Gluckman JC, Lagrange PH, Gicquel B, Neyrolles O. 2003. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J. Exp. Med. 197:121-127
9. Torrelles JB, Azad AK, Henning LN, Carlson TK, Schlesinger LS. 2008. Role of C-type lectins in mycobacterial infections. Curr. Drug Targets 9:102-112
10. Achkar JM, Casadevall A. 2013. Antibody-mediated immunity against tuberculosis: implications for vaccine development. Cell Host Microbe 13:250-262
11. Flynn JL. 2006. Lessons from experimental Mycobacterium tuberculosis infections. Microbes Infect. 8:1179-1188
12. Ernst JD. 2012. The immunological life cycle of tuberculosis. Nat. Rev. Immunol. 12:581-591
13. Cosma CL, Sherman DR, Ramakrishnan L. 2003. The secret lives of the pathogenic mycobacteria. Annu. Rev. Microbiol. 57:641-676
14. Ehrt S, Schnappinger D. 2009. Mycobacterial survival strategies in the phagosome: defence against host stresses. Cell. Microbiol. 11:1170-1178
15. Napier RJ, Rafi W, Cheruvu M, Powell KR, Zaunbrecher MA, Bornmann W, Salgame P, Shinnick TM, Kalman D. 2011. Imatinibsensitive tyrosine kinases regulate mycobacterial pathogenesis and represent therapeutic targets against tuberculosis. Cell Host Microbe 10: 475-485
16. Rohde K, Yates RM, Purdy GE, Russell DG. 2007. Mycobacterium tuberculosis and the environment within the phagosome. Immunol. Rev. 219:37-54
17. Vergne I, Chua J, Lee HH, Lucas M, Belisle J, Deretic V. 2005. Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 102:4033-4038
18. MacMicking JD. 2012. Interferon-inducible effector mechanisms in cell-autonomous immunity. Nat. Rev. Immunol. 12:367-382
19. Bruns H, Stegelmann F, Fabri M, Döhner K, van Zandbergen G, Wagner M, Skinner M, Modlin RL, Stenger S. 2012. Abelson tyrosine kinase controls phagosomal acidification required for killing of Mycobacterium tuberculosis in human macrophages. J. Immunol. 189:4069-4078
20. Rajni Meena LS. 2010. Guanosine triphosphatases as novel therapeutic targets in tuberculosis. Int. J. Infect. Dis. 14:e682- e687
21. Martens S, Howard J. 2006. The interferon-inducible GTPases. Annu. Rev. Cell Dev. Biol. 22:559-589
22. Haas AK, Fuchs E, Kopajtich R, Barr FA. 2005. A GTPase-activating protein controls Rab5 function in endocytic trafficking. Nat. Cell Biol. 7:887-893
23. Singh SB, Davis AS, Taylor GA, Deretic V. 2006. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313: 1438-1441
24. MacMicking JD, Taylor GA, McKinney JD. 2003. Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science 302:654-659
25. Feng CG, Collazo-Custodio CM, Eckhaus M, Hieny S, Belkaid Y, Elkins K, Jankovic D, Taylor GA, Sher A. 2004. Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia. J. Immunol. 172:1163-1168
26. Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JD. 2011. A family of IFN-inducible 65-kD GTPases protects against bacterial infection. Science 332:717-721
27. Deretic V. 2011. Autophagy in immunity and cell-autonomous defense against intracellular microbes. Immunol. Rev. 240:92-104
28. Songane M, Kleinnijenhuis J, Netea MG, van Crevel R. 2012. The role of autophagy in host defence against Mycobacterium tuberculosis infection. Tuberculosis (Edinb.) 92:388-396
29. Rubinsztein DC, Codogno P, Levine B. 2012. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat. Rev. Drug Discov. 11:709-730
30. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753-766
31. Harris J, De Haro SA, Master SS, Keane J, Roberts EA, Delgado M, Deretic V. 2007. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 27:505-517
32. Pilli M, Arko-Mensah J, Ponpuak M, Roberts E, Master S, Mandell MA, Dupont N, Ornatowski W, Jiang S, Bradfute SB, Bruun JA, Hansen TE, Johansen T, Deretic V. 2012. TBK-1 promotes autophagymediated antimicrobial defense by controlling autophagosome maturation. Immunity 37:223-234
33. Ponpuak M, Davis AS, Roberts EA, Delgado MA, Dinkins C, Zhao Z, Virgin HW, Kyei GB, Johansen T, Vergne I, Deretic V. 2010. Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity 32: 329-341
34. Kuijl C, Savage ND, Marsman M, Tuin AW, Janssen L, Egan DA, Ketema M, van den Nieuwendijk R, van den Eeden SJ, Geluk A, Poot A, van der Marel G, Beijersbergen RL, Overkleeft H, Ottenhoff TH, Neefjes J. 2007. Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1. Nature 450:725-730
35. Kumar D, Nath L, Kamal MA, Varshney A, Jain A, Singh S, Rao KV. 2010. Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell 140:731-743
36. Watson RO, Manzanillo PS, Cox JS. 2012. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 150:803-815
37. Kim JJ, Lee HM, Shin DM, Kim W, Yuk JM, Jin HS, Lee SH, Cha GH, Kim JM, Lee ZW, Shin SJ, Yoo H, Park YK, Park JB, Chung J, Yoshimori T, Jo EK. 2012. Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. Cell Host Microbe 11:457-468
38. de Carvalho LP, Lin G, Jiang X, Nathan C. 2009. Nitazoxanide kills replicating and nonreplicating Mycobacterium tuberculosis and evades resistance. J. Med. Chem. 52:5789-5792
39. Lam KK, Zheng X, Forestieri R, Balgi AD, Nodwell M, Vollett S, Anderson HJ, Andersen RJ, Av-Gay Y, Roberge M. 2012. Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular proliferation of Mycobacterium tuberculosis. PLoS Pathog. 8:e1002691. doi:10.1371/journal.ppat.1002691
40. Gold B, Pingle M, Brickner SJ, Shah N, Roberts J, Rundell M, Bracken WC, Warrier T, Somersan S, Venugopal A, Darby C, Jiang X, Warren JD, Fernandez J, Ouerfelli O, Nuermberger EL, Cunningham-Bussel A, Rath P, Chidawanyika T, Deng H, Realubit R, Glickman JF, Nathan CF. 2012. Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials. Proc. Natl. Acad. Sci. U. S. A. 109:16004-16011
41. Pinault L, Han JS, Kang CM, Franco J, Ronning DR. 2013. Zafirlukast inhibits complexation of Lsr2 with DNA and growth of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 57:2134-2140
42. Adams JS, Liu PT, Chun R, Modlin RL, Hewison M. 2007. Vitamin D in defense of the human immune response. Ann. N. Y. Acad. Sci. 1117: 94-105
43. Hewison M. 2011. Antibacterial effects of vitamin D. Nat. Rev. Endocrinol. 7:337-345
44. Krutzik SR, Hewison M, Liu PT, Robles JA, Stenger S, Adams JS, Modlin RL. 2008. IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. J. Immunol. 181:7115-7120
45. Anand SP, Selvaraj P. 2009. Effect of 1,25 dihydroxyvitamin D(3) on matrix metalloproteinases MMP-7, MMP-9 and the inhibitor TIMP-1 in pulmonary tuberculosis. Clin. Immunol. 133:126-131
46. Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, Lee HM, Krutzik SR, Schenk M, Sieling PA, Teles R, Montoya D, Iyer SS, Bruns H, Lewinsohn DM, Hollis BW, Hewison M, Adams JS, Steinmeyer A, Zugel U, Cheng G, Jo EK, Bloom BR, Modlin RL. 2011. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci. Transl. Med. 3:104ra102. doi:10.1126/scitranslmed .3003045
47. Liu PT, Krutzik SR, Modlin RL. 2007. Therapeutic implications of the TLR and VDR partnership. Trends Mol. Med. 13:117-124
48. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS,Bloom BR, Modlin RL. 2006. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770-1773
49. Liu PT, Stenger S, Tang DH, Modlin RL. 2007. Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J. Immunol. 179:2060-2063
50. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH, Kim JM, Jo EK. 2009. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 6:231-243
51. Wilkinson R, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, Wright D, Latif M, Davidson R. 2000. Influence of vitamin D receptor and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet 355:618-621
52. Martineau AR, Newton SM, Wilkinson KA, Kampmann B, Hall BM, Nawroly N, Packe GE, Davidson RN, Griffiths CJ, Wilkinson RJ. 2007. Neutrophil-mediated innate immune resistance to mycobacteria. J. Clin. Invest. 117:1988-1994
53. Nursyam EW, Amin Z, Rumende CM. 2006. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med. Indones. 38:3-5
54. Kota SK, Jammula S, Kota SK, Tripathy PR, Panda S, Modi KD. 2011. Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis. Diabetes Metab. Syndr. 5:85-89
55. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Woodward NJ, Venton TR, Barnes KE, Mullett CJ, Coussens AK, Rutterford CM, Mein CA, Davies GR, Wilkinson RJ, Nikolayevskyy V, Drobniewski FA, Eldridge SM, Griffiths CJ. 2011. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 377:242-250
56. Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, Timms PM, Venton TR, Bothamley GH, Packe GE, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Mein CA, Bhaw-Rosun L, Nuamah R, Young DB, Drobniewski FA, Griffiths CJ, Martineau AR. 2012. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc. Natl. Acad. Sci. U. S. A. doi:10.1073/pnas.1200072109
57. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, Andersen PL, Glerup H, Sodemann M. 2009. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebocontrolled trial. Am. J. Respir. Crit. Care Med. 179:843-850
58. Singh V, Jamwal S, Jain R, Verma P, Gokhale R, Rao KV. 2012. Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype. Cell Host Microbe 12:669-681
59. Almeida PE, Silva AR, Maya-Monteiro CM, Töröcsik D, D'Avila H, Dezsö B, Magalhães KG, Castro-Faria-Neto HC, Nagy L, Bozza PT. 2009. Mycobacterium bovis bacillus Calmette-Guérin infection induces TLR2-dependent peroxisome proliferator-activated receptor gamma expression and activation: functions in inflammation, lipid metabolism, and pathogenesis. J. Immunol. 183:1337-1345
60. Mahajan S, Dkhar HK, Chandra V, Dave S, Nanduri R, Janmeja AK, Agrewala JN, Gupta P. 2012. Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPAR and TR4 for survival. J. Immunol. 188:5593-5603
61. Rajaram MV, Brooks MN, Morris JD, Torrelles JB, Azad AK, Schlesinger LS. 2010. Mycobacterium tuberculosis activates human macrophage peroxisome proliferator-activated receptor gamma linking mannose receptor recognition to regulation of immune responses. J. Immunol. 185:929-942
62. Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, Grimaldi PA, Kadowaki T, Lazar MA, O'Rahilly S, Palmer CN, Plutzky J, Reddy JK, Spiegelman BM, Staels B, Wahli W. 2006. International Union of Pharmacology. LXI. Peroxisome proliferatoractivated receptors. Pharmacol. Rev. 58:726-741
63. Almeida PE, Carneiro AB, Silva AR, Bozza. PT 2012. PPAR expression and function in mycobacterial infection: roles in lipid metabolism, immunity, and bacterial killing. PPAR Res. 2012:383829
64. Korf H, Vander Beken S, Romano M, Steffensen KR, Stijlemans B, Gustafsson JA, Grooten J, Huygen K. 2009. Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice. J. Clin. Invest. 119:1626-1637
65. Staels B, Fruchart JC. 2005. Therapeutic roles of peroxisome proliferator- activated receptor agonists. Diabetes 54:2460-2470
66. Duan L, Gan H, Arm J, Remold HG. 2001. Cytosolic phospholipase A2 participates with TNF-alpha in the induction of apoptosis of human macrophages infected with Mycobacterium tuberculosis H37Ra. J. Immunol. 166:7469-7476
67. Akaki T, Tomioka H, Shimizu T, Dekio S, Sato K. 2000. Comparative roles of free fatty acids with reactive nitrogen intermediates and reactive oxygen intermediates in expression of the anti-microbial activity of macrophages against Mycobacterium tuberculosis. Clin. Exp. Immunol. 121: 302-310
68. Vandal OH, Gelb MH, Ehrt S, Nathan CF. 2006. Cytosolic phospholipase A2 enzymes are not required by mouse bone marrow-derived macrophages for the control of Mycobacterium tuberculosis in vitro. Infect. Immun. 74:1751-1756
69. Kusner DJ, Barton JA. 2001. ATP stimulates human macrophages to kill intracellular virulent Mycobacterium tuberculosis via calciumdependent phagosome-lysosome fusion. J. Immunol. 167:3308-3315
70. Auricchio G, Garg SK, Martino A, Volpe E, Ciaramella A, De Vito P, Baldini PM, Colizzi V, Fraziano M. 2003. Role of macrophage phospholipase D in natural and CpG-induced antimycobacterial activity. Cell. Microbiol. 5:913-920
71. Garg SK, Valente E, Greco E, Santucci MB, De Spirito M, Papi M, Bocchino M, Saltini C, Fraziano M. 2006. Lysophosphatidic acid enhances antimycobacterial activity both in vitro and ex vivo. Clin. Immunol. 121:23-28
72. Garg SK, Volpe E, Palmieri G, Mattei M, Galati D, Martino A, Piccioni MS, Valente E, Bonanno E, De Vito P, Baldini PM, Spagnoli LG, Colizzi V, Fraziano M. 2004. Sphingosine 1-phosphate induces antimicrobial activity both in vitro and in vivo. J. Infect. Dis. 189:2129-2138
73. Greco E, Santucci MB, Quintiliani G, Papi M, De Spirito M, Fraziano M. 2009. CpG oligodeoxynucleotides promote phospholipase D dependent phagolysosome maturation and intracellular mycobacterial killing in M. tuberculosis infected type II alveolar epithelial cells. Cell. Immunol. 259:1-4
74. Campbell EL, Serhan CN, Colgan SP. 2011. Antimicrobial aspects of inflammatory resolution in the mucosa: a role for proresolving mediators. J. Immunol. 187:3475-3481
75. Serhan CN. 2007. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu. Rev. Immunol. 25:101-137
76. Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB. 1986. Arachidonic acid metabolism. Annu. Rev. Biochem. 55:69-102
77. Spector AA, Fang X, Snyder GD, Weintraub NL. 2004. Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog. Lipid Res. 43:55-90
78. Behar SM, Divangahi M, Remold HG. 2010. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? Nat. Rev. Microbiol. 8:668-674
79. Chen M, Divangahi M, Gan H, Shin DS, Hong S, Lee DM, Serhan CN, Behar SM, Remold HG. 2008. Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J. Exp. Med. 205:2791-2801
80. Divangahi M, Desjardins D, Nunes-Alves C, Remold HG, Behar SM. 2010. Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis. Nat. Immunol. 11:751-758
81. Greco E, Quintiliani G, Santucci MB, Serafino A, Ciccaglione AR, Marcantonio C, Papi M, Maulucci G, Delogu G, Martino A, Goletti D, Sarmati L, Andreoni M, Altieri A, Alma M, Caccamo N, Di Liberto D, De Spirito M, Savage ND, Nisini R, Dieli F, Ottenhoff TH, Fraziano M. 2012. Janus-faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. U. S. A. 109:E1360-E1368
82. Tobin DM, Vary JC, Jr, Ray JP, Walsh GS, Dunstan SJ, Bang ND, Hagge DA, Khadge S, King MC, Hawn TR, Moens CB, Ramakrishnan L. 2010. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140:717-730
83. Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT, Vary JC, Hawn TR, Dunstan SJ, Farrar JJ, Thwaites GE, King MC, Serhan CN, Ramakrishnan L. 2012. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections Cell 148:434-446
84. Curtis J, Kopanitsa L, Stebbings E, Speirs A, Ignatyeva O, Balabanova Y, Nikolayevskyy V, Hoffner S, Horstmann R, Drobniewski F, Nejentsev S. 2011. Association analysis of the LTA4H gene polymorphisms and pulmonary tuberculosis in 9115 subjects. Tuberculosis (Edinb.) 91: 22-25
85. Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, Nguyen QH, Nguyen TT, Nguyen NH, Nguyen TN, Nguyen NL, Nguyen HD, Vu NT, Cao HH, Tran TH, Pham PM, Nguyen TD, Stepniewska K, White NJ, Tran TH, Farrar JJ. 2004. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N. Engl. J. Med. 351:1741-1751
86. Clish CB, O'Brien JA, Gronert K, Stahl GL, Petasis NA, Serhan CN. 1999. Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo. Proc. Natl. Acad. Sci. U. S. A. 96:8247-8252
87. Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S. 2000. Lipoxin A4 inhibits IL-1 beta-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J. Immunol. 164:2660-2666
88. Aliberti J, Serhan C, Sher A. 2002. Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection. J. Exp. Med. 196:1253-1262
89. Aliberti J, Hieny S, CReis e Sousa Serhan CN, Sher A. 2002. Lipoxinmediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity. Nat. Immunol. 3:76-82
90. Bafica A, Scanga CA, Serhan C, Machado F, White S, Sher A, Aliberti J. 2005. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J. Clin. Invest. 115:1601-1606
91. Peres CM, de Paula L, Medeiros AI, Sorgi CA, Soares EG, Carlos D, Peters-Golden M, Silva CL, Faccioli LH. 2007. Inhibition of leukotriene biosynthesis abrogates the host control of Mycobacterium tuberculosis. Microbes Infect. 9:483-489
92. Herb F, Thye T, Niemann S, Browne EN, Chinbuah MA, Gyapong J, Osei I, Owusu-Dabo E, Werz O, Rusch-Gerdes S, Horstmann RD, Meyer CG. 2008. ALOX5 variants associated with susceptibility to human pulmonary tuberculosis. Hum. Mol. Genet. 17:1052-1060
93. Schoeman JF, Janse van Rensburg A, Laubscher JA, Springer P. 2011. The role of aspirin in childhood tuberculous meningitis. J. Child Neurol. 26:956-962
94. Misra UK, Kalita J, Nair PP. 2010. Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial. J. Neurol. Sci. 293:12-17
95. Vilaplana C, Marzo E, Tapia G, Diaz J, Garcia V, Cardona PJ. 2013. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J. Infect. Dis. 208:199-202
96. Byrne ST, Denkin SM, Zhang Y. 2007. Aspirin and ibuprofen enhance pyrazinamide treatment of murine tuberculosis. J. Antimicrob. Chemother. 59:313-316
97. Byrne ST, Denkin SM, Zhang Y. 2007. Aspirin antagonism in isoniazid treatment of tuberculosis in mice. Antimicrob. Agents Chemother. 51: 794-795
98. Dutta NK, Mazumdar K, Dastidar SG, Park JH. 2007. Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice. Int. J. Antimicrob. Agents 30:336-340
99. Ivanyi J, Zumla A. 2013. Nonsteroidal antiinflammatory drugs for adjunctive tuberculosis treatment. J. Infect. Dis. 208:185-188
100. Wu K, Koo J, Jiang X, Chen R, Cohen SN, Nathan C. 2012. Improved control of tuberculosis and activation of macrophages in mice lacking protein kinase R. PLoS One 7:e30512. doi:10.1371/journal.pone.0030512
101. Bando Y, Onuki R, Katayama T, Manabe T, Kudo T, Taira K, Tohyama M. 2005. Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease. Neurochem. Int. 46:11-18 involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease
102. Chang RC, Suen KC, Ma CH, Elyaman W, Ng HK, Hugon J. 2002. Involvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2alpha in neuronal degeneration. J. Neurochem. 83:1215-1225
103. Goodman AG, Fornek JL, Medigeshi GR, Perrone LA, Peng X, Dyer MD, Proll SC, Knoblaugh SE, Carter VS, Korth MJ, Nelson JA, Tumpey TM, Katze MG. 2009. P58(IPK): a novel "CIHD" member of the host innate defense response against pathogenic virus infection. PLoS Pathog. 5:e1000438. doi:10.1371/journal.ppat.1000438
104. Hu JH, Zhang H, Wagey R, Krieger C, Pelech SL. 2003. Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord. J. Neurochem. 85:432-442
105. Morel M, Couturier J, Lafay-Chebassier C, Paccalin M, Page G. 2009. PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer's disease. J. Cell. Mol. Med. 13:1476-1488
106. Johnson EE, Wessling-Resnick M. 2012. Iron metabolism and the innate immune response to infection. Microbes Infect. 14:207-216
107. Hoette TM, Clifton MC, Zawadzka AM, Holmes MA, Strong RK, Raymond KN. 2011. Immune interference in Mycobacterium tuberculosis intracellular iron acquisition through siderocalin recognition of carboxymycobactins. ACS Chem. Biol. 6:1327-1331
108. Holmes MA, Paulsene W, Jide X, Ratledge C, Strong RK. 2005. Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. Structure 13:29-41
109. Halaas O, Steigedal M, Haug M, Awuh JA, Ryan L, Brech A, Sato S Husebye H, Cangelosi GA, Akira S, Strong RK, Espevik T, Flo TH. 2010. Intracellular Mycobacterium avium intersect transferrin in the Rab11(+) recycling endocytic pathway and avoid lipocalin 2 trafficking to the lysosomal pathway. J. Infect. Dis. 201:783-792
110. Saiga H, Nishimura J, Kuwata H, Okuyama M, Matsumoto S, Sato S, Matsumoto M, Akira S, Yoshikai Y, Honda K, Yamamoto M, Takeda K. 2008. Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium. J. Immunol. 181:8521-8527
111. . 111. Skamene E, Schurr E, Gros P. 1998. Infection genomics: Nramp1 as a major determinant of natural resistance to intracellular infections. Annu. Rev. Med. 49:275-287
112. Li X, Yang Y, Zhou F, Zhang Y, Lu H, Jin Q, Gao L. 2011. SLC11A1 (NRAMP1) polymorphisms and tuberculosis susceptibility: updated systematic review and meta-analysis. PLoS One 6:e15831. doi:10.1371 /journal.pone.0015831
113. Govoni G, Gros P. 1998. Macrophage NRAMP1 and its role in resistance to microbial infections. Inflamm. Res. 47:277-284
114. Vidal S, Tremblay ML, Govoni G, Gauthier S, Sebastiani G, Malo D, Skamene E, Olivier M, Jothy S, Gros P. 1995. The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J. Exp. Med. 182:655-666
115. North RJ, LaCourse R, Ryan L, Gros P. 1999. Consequence of Nramp1 deletion to Mycobacterium tuberculosis infection in mice. Infect. Immun. 67:5811-5814
116. Sow FB, Alvarez GR, Gross RP, Satoskar AR, Schlesinger LS, Zwilling BS, Lafuse WP. 2009. Role of STAT1, NF-kappaB, and C/EBPbeta in the macrophage transcriptional regulation of hepcidin by mycobacterial infection and IFN-gamma. J. Leukoc. Biol. 86:1247-1258
117. Sow FB, Nandakumar S, Velu V, Kellar KL, Schlesinger LS, Amara RR, Lafuse WP, Shinnick TM, Sable SB. 2011. Mycobacterium tuberculosis components stimulate production of the antimicrobial peptide hepcidin. Tuberculosis (Edinb.) 91:314-321
118. Johnson EE, Sandgren A, Cherayil BJ, Murray M, Wessling-Resnick M. 2010. Role of ferroportin in macrophage-mediated immunity. Infect. Immun. 78:5099-5106
119. Welsh KJ, Hwang SA, Boyd S, Kruzel ML, Hunter RL, Actor JK. 2011 Influence of oral lactoferrin on Mycobacterium tuberculosis induced immunopathology. Tuberculosis (Edinb.) 91(Suppl 1):S105-S113
120. Gerosa F, Baldani-Guerra B, Lyakh LA, Batoni G, Esin S, Winkler- Pickett RT, Consolaro MR, De Marchi M, Giachino D, Robbiano A, Astegiano M, Sambataro A, Kastelein RA, Carra G, Trinchieri G. 2008. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J. Exp. Med. 205:1447-1461
121. Lutz M, Knaus P. 2002. Integration of the TGF-beta pathway into the cellular signalling network. Cell Signal. 14:977-988
122. Manel N, Unutmaz D, Littman DR. 2008. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction o the nuclear receptor RORgammat. Nat. Immunol. 9:641-649
123. Ramos HJ, Davis AM, Cole AG, Schatzle JD, Forman J, Farrar JD. 2009. Reciprocal responsiveness to interleukin-12 and interferon-alpha specifies human CD8 effector versus central memory T-cell fates. Blood 113:5516-5525
124. Trinchieri G. 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3:133-146
125. Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupe P, Barillot E, Soumelis V. 2008. A critical function for transforming growth factorbeta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat. Immunol. 9:650-657
126. Antonelli LR, Gigliotti Rothfuchs A, Goncalves R, Roffe E, Cheever AW, Bafica A, Salazar AM, Feng CG, Sher A. 2010. Intranasal poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population. J. Clin. Invest. 120:1674-1682
127. Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, Komisopoulou E, Kelly-Scumpia K, Chun R, Iyer SS, Sarno EN, Rea TH, Hewison M, Adams JS, Popper SJ, Relman DA, Stenger S, BloomBR, Cheng G, Modlin RL. 2013. Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science 339: 1448-1453
128. Redford PS, Boonstra A, Read S, Pitt J, Graham C, Stavropoulos E, Bancroft GJ, O'Garra A. 2010. Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung. Eur. J. Immunol. 40:2200- 2210
129. Redford PS, Murray PJ, O'Garra A. 2011. The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol. 4:261- 270
130. Kursar M, Koch M, Mittrucker HW, Nouailles G, Bonhagen K, Kamradt T, Kaufmann SH. 2007. Regulatory T cells prevent efficient clearance of Mycobacterium tuberculosis. J. Immunol. 178:2661-2665
131. Larson RP, Shafiani S, Urdahl KB. 2013. Foxp3(+) regulatory T cells in tuberculosis. Adv. Exp. Med. Biol. 783:165-180
132. Davis JM, Ramakrishnan L. 2009. The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell 136:37-49
133. Ehrt S, Schnappinger D, Bekiranov S, Drenkow J, Shi S, Gingeras TR, Gaasterland T, Schoolnik G, Nathan C. 2001. Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase. J. Exp. Med. 194:1123-1140
134. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. 1993. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178:2249-2254
135. Casanova JL, Abel L. 2002. Genetic dissection of immunity to mycobacteria: the human model. Annu. Rev. Immunol. 20:581-620
136. Condos R, Raju B, Canova A, Zhao BY, Weiden M, Rom WN, Pine R. 2003. Recombinant gamma interferon stimulates signal transduction and gene expression in alveolar macrophages in vitro and in tuberculosis patients. Infect. Immun. 71:2058-2064
137. Milanés-Virelles MT, García-García I, Santos-Herrera Y, Valdés- Quintana M, Valenzuela-Silva CM, Jiménez-Madrigal G, Ramos- Gómez TI, Bello-Rivero I, Fernández-Olivera N, Sánchez-de la Osa RB, Rodríguez-Acosta C, González- Méndez L, Martínez-Sánchez G, López-Saura PA, MACGAM Study Group. 2008. Adjuvant interferon gamma in patients with pulmonary atypical mycobacteriosis: a randomized, double-blind, placebo-controlled study. BMC Infect. Dis. 8:17. doi: 10.1186/1471-2334-8-17
138. Dawson R, Condos R, Tse D, Huie ML, Ress S, Tseng CH, Brauns C, Weiden M, Hoshino Y, Bateman E, Rom WN. 2009. Immunomodulation with recombinant interferon-gamma1b in pulmonary tuberculosis. PLoS One 4:e6984. doi:10.1371/journal.pone.0006984
139. Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ, Schreiber R, Mak TW, Bloom BR. 1995. Tumor necrosis factoralpha is required in the protective immune response against Mycobacteriumtuberculosis in mice. Immunity 2:561-572
140. Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, Kampmann B, Hellmich B, Groves R, Schreiber S, Wallis RS, Sotgiu G, Scholvinck EH, Goletti D, Zellweger JP, Diel R, Carmona L, Bartalesi F, Ravn P, Bossink A, Duarte R, Erkens C, Clark J, Migliori GB, Lange C. 2010. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur. Respir. J. 36: 1185-1206
141. Wallis RS. 2005. Reconsidering adjuvant immunotherapy for tuberculosis. Clin. Infect. Dis. 41:201-208
142. Wallis RS, Kyambadde P, Johnson JL, Horter L, Kittle R, Pohle M, Ducar C, Millard M, Mayanja-Kizza H, Whalen C, Okwera A. 2004. A study of the safety, immunology, virology, and microbiology of adjunctiveetanercept in HIV-1-associated tuberculosis. AIDS 18:257-264
143. Corral LG, Kaplan G. 1999. Immunomodulation by thalidomide and thalidomide analogues. Ann. Rheum. Dis. 58(Suppl 1):I107-I113
144. Maiga M, Agarwal N, Ammerman NC, Gupta R, Guo H, Maiga MC, Lun S, Bishai WR. 2012. Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model. PLoS One 7:e30749. doi:10.1371 /journal.pone.0030749
145. Kalamidas SA, Kuehnel MP, Peyron P, Rybin V, Rauch S, Kotoulas OB, Houslay M, Hemmings BA, Gutierrez MG, Anes E, Griffiths G. 2006. cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: consequences for mycobacteria. J. Cell Sci. 119:3686-3694.
146. Agarwal N, Lamichhane G, Gupta R, Nolan S, Bishai WR. 2009. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature 460:98-102
147. Schoeman JF, Springer P, van Rensburg AJ, Swanevelder S, Hanekom WA, Haslett PA, Kaplan G. 2004. Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J. Child Neurol. 19:250-257
148. Koo MS, Manca C, Yang G, O'Brien P, Sung N, Tsenova L, Subbian S, Fallows D, Muller G, Ehrt S, Kaplan G. 2011. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice. PLoS One 6:e17091. doi:10.1371/journal.pone. 0017091
149. Subbian S, Tsenova L, O'Brien P, Yang G, Koo MS, Peixoto B, Fallows D, Dartois V, Muller G, Kaplan G. 2011. Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs. PLoS Pathog. 7:e1002262. doi:10.1371/journal.ppat. 1002262
150. Subbian S, Tsenova L, O'Brien P, Yang G, Koo MS, Peixoto B, Fallows D, Zeldis JB, Muller G, Kaplan G. 2011. Phosphodiesterase-4 inhibition combined with isoniazid treatment of rabbits with pulmonary tuberculosis reduces macrophage activation and lung pathology. Am. J. Pathol. 179:289-301
151. Maiga M, Ammerman NC, Maiga MC, Tounkara A, Siddiqui S, Polis M, Murphy R, Bishai WR. 2013. Adjuvant host-directed therapy with types 3 and 5 but not type 4 phosphodiesterase inhibitors shortens the duration of tuberculosis treatment. J. Infect. Dis. 208:512-519
152. Wallis RS, Nsubuga P, Whalen C, Mugerwa RD, Okwera A, Oette D, Jackson JB, Johnson JL, Ellner JJ. 1996. Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a randomized, controlled trial. J. Infect. Dis. 174:727-733
153. Strang JI, Kakaza HH, Gibson DG, Girling DJ, Nunn AJ, Fox W. 1987. Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei. Lancet ii:1418-1422
154. Simmons CP, Thwaites GE, Quyen NT, Torok E, Hoang DM, Chau TT, Mai PP, Lan NT, Dung NH, Quy HT, Bang ND, Hien TT, Farrar J. 2006. Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. J. Immunol. 176 2007-2014
155. Roca FJ, Ramakrishnan L. 2013. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell 153:521-534
156. Elkington P, Shiomi T, Breen R, Nuttall RK, Ugarte-Gil CA, Walker NF, Saraiva L, Pedersen B, Mauri F, Lipman M, Edwards DR, Robertson BD, D'Armiento J, Friedland JS. 2011. MMP-1 drives immunopathology in human tuberculosis and transgenic mice. J. Clin. Invest. 121:1827-1833
157. Clutterbuck AL, Asplin KE, Harris P, Allaway D, Mobasheri A. 2009. Targeting matrix metalloproteinases in inflammatory conditions. Curr. Drug Targets 10:1245-1254
158. Coussens A, Timms PM, Boucher BJ, Venton TR, Ashcroft AT, Skolimowska KH, Newton SM, Wilkinson KA, Davidson RN, Griffiths CJ, Wilkinson RJ, Martineau AR. 2009. 1,25-Dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection. Immunology 127:539-548
159. Elkington PT, Emerson JE, Lopez-Pascua LD, O'Kane CM, Horncastle DE, Boyle JJ, Friedland JS. 2005. Mycobacterium tuberculosis upregulates matrix metalloproteinase-1 secretion from human airway epithelial cells via a p38 MAPK switch. J. Immunol. 175:5333-5340
160. Gurusamy N, Das DK. 2009. Autophagy, redox signaling, and ventricular remodeling. Antioxid. Redox Signal. 11:1975-1988
161. Parks WC, Wilson CL, López-Boado YS. 2004. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat. Rev. Immunol. 4:617-629
162. Kumar D, Kumar M, Saravanan C, Singh SK. 2012. Curcumin: a potential candidate for matrix metalloproteinase inhibitors. Expert Opin. Ther. Targets 16:959-972
163. Friedland JS, Shaw TC, Price NM, Dayer JM. 2002. Differential regulation of MMP-1/9 and TIMP-1 secretion in human monocytic cells in response to Mycobacterium tuberculosis. Matrix Biol. 21:103-110
164. Quiding-Jarbrink M, Smith DA, Bancroft GJ. 2001. Production of matrix metalloproteinases in response to mycobacterial infection. Infect. Immun. 69:5661-5670
165. Green JA, Tran CT, Farrar JJ, Nguyen MT, Nguyen PH, Dinh SX, Ho ND, Ly CV, Tran HT, Friedland JS, Thwaites GE. 2009. Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis. PLoS One 4:e7277. doi:10 .1371/journal.pone.0007277
166. Price NM, Gilman RH, Uddin J, Recavarren S, Friedland JS. 2003 Unopposed matrix metalloproteinase-9 expression in human tuberculous granuloma and the role of TNF-alpha-dependent monocyte networks. J. Immunol. 171:5579-5586
167. Taylor JL, Hattle JM, Dreitz SA, Troudt JM, Izzo LS, Basaraba RJ, Orme IM, Matrisian LM, Izzo AA. 2006. Role for matrix metalloproteinase 9 in granuloma formation during pulmonary Mycobacterium tuberculosis infection. Infect. Immun. 74:6135-6144
168. Volkman HE, Pozos TC, Zheng J, Davis JM, Rawls JF, Ramakrishnan L. 2010. Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science 327:466-469
169. Hernandez-Pando. 2000. Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent metalloproteinases, causes deviation of the cytokine profile towards type-2 in experimental pulmonary tuberculosis in Balb/c mice. J. Exp. Pathol. 81:199-209
170. Izzo AA, Izzo LS, Kasimos J, Majka S. 2004. A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection. Tuberculosis (Edinb.) 84:387-396
171. Nathan C. 2006. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol. 6:173-182
172. Yang CT, Cambier CJ, Davis JM, Hall CJ, Crosier PS, Ramakrishnan L. 2012. Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages. Cell Host Microbe 12:301-312
173. Eum SY, Kong JH, Hong MS, Lee YJ, Kim JH, Hwang SH, Cho SN, Via LE, Barry CE, III. 2010. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB.Chest 137:122-128
174. Repasy T, Lee J, Marino S, Martinez N, Kirschner DE, Hendricks G, Baker S, Wilson AA, Kotton DN, Kornfeld H. 2013. Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo. PLoS Pathog. 9:e1003190. doi:10.1371/journal.ppat.1003190
175. Nathan C. 2002. Points of control in inflammation. Nature 420:846- 852
176. Lowe DM, Redford PS, Wilkinson RJ, O'Garra A, Martineau AR. 2012. Neutrophils in tuberculosis: friend or foe? Trends Immunol. 33:14-25
177. Burgos RA, Hidalgo MA, Figueroa CD, Conejeros I, Hancke JL. 2009. New potential targets to modulate neutrophil function in inflammation. Mini Rev. Med. Chem. 9:153-168
178. Goldmann O, Medina E. 2012. The expanding world of extracellular traps: not only neutrophils but much more. Front. Immunol. 3:420.
179. Ramos-Kichik V, Mondragon-Flores R, Mondragon-Castelan M, Gonzalez- Pozos S, Muniz-Hernandez S, Rojas-Espinosa O, Chacon-Salinas R, Estrada-Parra S, Estrada-Garcia I. 2009. Neutrophil extracellular traps are induced by Mycobacterium tuberculosis. Tuberculosis (Edinb.) 89:29-37
180. Wong KW, Jacobs WR, Jr. 2013. Mycobacterium tuberculosis exploits human interferon gamma to stimulate macrophage extracellular trap formation and necrosis. J. Infect. Dis. doi:10.1093/infdis/jit097
181. Cheng OZ, Palaniyar N. 2013. NET balancing: a problem in inflammatory lung diseases. Front. Immunol. 4:1
182. Kaplan MJ, Radic M. 2012. Neutrophil extracellular traps: doubleedged swords of innate immunity. J. Immunol. 189:2689-2695
183. Ramakrishnan L. 2012. Revisiting the role of the granuloma in tuberculosis. Nat. Rev. Immunol. 12:352-366
184. Dheda K, Booth H, Huggett JF, Johnson MA, Zumla A, Rook GA. 2005. Lung remodeling in pulmonary tuberculosis. J. Infect. Dis. 192: 1201-1209
185. Adamali HI, Maher TM. 2012. Current and novel drug therapies for idiopathic pulmonary fibrosis. Drug Des. Dev. Ther. 6:261-271
186. Hakim A, Adcock IM, Usmani OS. 2012. Corticosteroid resistance and novel anti-inflammatory therapies in chronic obstructive pulmonary disease: current evidence and future direction. Drugs 72:1299-1312
187. Royce SG, Cheng V, Samuel CS, Tang ML. 2012. The regulation of fibrosis in airway remodeling in asthma. Mol. Cell. Endocrinol. 351:167-175
188. Maher TM. 2010. Pirfenidone in idiopathic pulmonary fibrosis. Drugs Today (Barc.) 46:473-482
189. Moore B, Murphy RF, Agrawal DK. 2008. Interaction of TGF-beta with immune cells in airway disease. Curr. Mol. Med. 8:427-436
190. Hancock A, Armstrong L, Gama R, Millar A. 1998. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am. J. Respir. Cell Mol. Biol. 18:60-65
191. Rose CE, Jr, Sung SS, Fu SM. 2003. Significant involvement of CCL2 (MCP-1) in inflammatory disorders of the lung. Microcirculation 10: 273-288
192. Bennett RG. 2009. Relaxin and its role in the development and treatment of fibrosis. Transl. Res. 154:1-6
193. Allen JT, Spiteri MA. 2002. Growth factors in idiopathic pulmonary fibrosis: relative roles. Respir. Res. 3:13. doi:10.1186/rr162
194. Aono Y, Nishioka Y, Inayama M, Ugai M, Kishi J, Uehara H, Izumi K, Sone S. 2005. Imatinib as a novel antifibrotic agent in bleomycininduced pulmonary fibrosis in mice. Am. J. Respir. Crit. Care Med. 171: 1279-1285
195. Aysola RS, Hoffman EA, Gierada D, Wenzel S, Cook-Granroth J, Tarsi J, Zheng J, Schechtman KB, Ramkumar TP, Cochran R, Xueping E, Christie C, Newell J, Fain S, Altes TA, Castro M. 2008. Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology. Chest 134:1183-1191
196. Via LE, Schimel D, Weiner DM, Dartois V, Dayao E, Cai Y, Yoon YS, Dreher MR, Kastenmayer RJ, Laymon CM, Carny JE, Flynn JL, Herscovitch P, Barry CE, III. 2012. Infection dynamics and response to chemotherapy in a rabbit model of tuberculosis using [(1)(8)F]2-fluorodeoxy- D-glucose positron emission tomography and computed tomography. Antimicrob. Agents Chemother. 56:4391-4402
197. Pirofski LA, Casadevall A. 2008. The damage-response framework of microbial pathogenesis and infectious diseases. Adv. Exp. Med. Biol. 635: 135-146
198. Jayaswal S, Kamal MA, Dua R, Gupta S, Majumdar T, Das G, Kumar D, Rao KV. 2010. Identification of host-dependent survival factors for intracellular Mycobacterium tuberculosis through an siRNA screen. PLoS Pathog. 6:e1000839. doi:10.1371/journal.ppat.1000839
199. Bryk R, Wu K, Raimundo BC, Boardman PE, Chao P, Conn GL, Anderson E, Cole JL, Duffy NP, Nathan C, Griffin JH. 2011. Identification of new inhibitors of protein kinase R guided by statistical modeling. Bioorg. Med. Chem. Lett. 21:4108-4114.
200. Martineau AR, Wilkinson RJ, Wilkinson KA, Newton SM, Kampmann B, Hall BM, Packe GE, Davidson RN, Eldridge SM, Maunsell ZJ, Rainbow SJ, Berry JL, Griffiths CJ. 2007. A single dose of vitamin D enhances immunity to mycobacteria. Am. J. Respir. Crit. Care Med. 176: 208-213
201. Yamshchikov AV, Desai NS, Blumberg HM, Ziegler TR, Tangpricha V. 2009. Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials. Endocr. Pract. 15: 438-449.
202. Condos R, Rom WN, Schluger NW. 1997. Treatment of multidrugresistant pulmonary tuberculosis with interferon-gamma via aerosol. Lancet 349:1513-1515. Host-Directed Therapeutics for TB December