Monocyte/macrophage inflammatory response pathways to combat Francisella infection: Possible therapeutic targets?

Frontiers in Cellular and Infection Microbiology

Volumn 5, Issue FEB, 2014, Pages

  Gillette, Devyn D ^a   Tridandapani, Susheela ^a   Butchar, Jonathan P ^a  

^a THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

Author keywords

Francisella; Host response; Macrophages; Monocytes; Signaling

Indexed keywords

ANTIBIOTIC AGENT; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INFLAMMASOME; INTERFERON; INTERLEUKIN 1BETA CONVERTING ENZYME; PHOSPHATIDYLINOSITOL 3 KINASE; RAS PROTEIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; TOLL LIKE RECEPTOR 2; AUTACOID;

BACTERIAL CLEARANCE; BACTERIAL LOAD; FRANCISELLA PHILOMIRAGIA; FRANCISELLA TULARENSIS; INFLAMMATION; MACROPHAGE; MONOCYTE; NONHUMAN; REVIEW; TULAREMIA; FRANCISELLA; HOST PATHOGEN INTERACTION; HUMAN; IMMUNE RESPONSE; IMMUNOLOGY; METABOLISM; MICROBIOLOGY; SIGNAL TRANSDUCTION; SIGNALING;

FRANCISELLA; HOST RESPONSE; MACROPHAGES; MONOCYTES; SIGNALING;

FRANCISELLA TULARENSIS; HOST-PATHOGEN INTERACTIONS; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; MACROPHAGES; MONOCYTES; SIGNAL TRANSDUCTION;

EID: 84897917994     PISSN: None     EISSN: 22352988     Source Type: Journal    
DOI: 10.3389/fcimb.2014.00018     Document Type: Review

References (124)

1. Ahonen, C. L., Gibson, S. J., Smith, R. M., Pederson, L. K., Lindh, J. M., Tomai, M. A., et al. (1999). Dendritic cell maturation and subsequent enhanced T-cell stimulation induced with the novel synthetic immune response modifier R-848. Cell Immunol. 197, 62-72. doi: 10.1006/cimm.1999.1555.
2. Al Khodor, S., and Abu, K. Y. (2010). Triggering Ras signalling by intracellular Francisella tularensis through recruitment of PKCalpha and betaI to the SOS2/GrB2 complex is essential for bacterial proliferation in the cytosol. Cell Microbiol. 12, 1604-1621. doi: 10.1111/j.1462-5822.2010.01494.x.
3. Allen, L. A., Beecher, B. R., Lynch, J. T., Rohner, O. V., and Wittine, L. M. (2005). Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release. J. Immunol. 174, 3658-3667.
4. Anthony, L. S., Ghadirian, E., Nestel, F. P., and Kongshavn, P. A. (1989). The requirement for gamma interferon in resistance of mice to experimental tularemia. Microb. Pathog. 7, 421-428. doi: 10.1016/0882-4010(89)90022-3.
5. Anthony, L. S., Morrissey, P. J., and Nano, F. E. (1992). Growth inhibition of Francisella tularensis live vaccine strain by IFN-gamma-activated macrophages is mediated by reactive nitrogen intermediates derived from L-arginine metabolism. J. Immunol. 148, 1829-1834.
6. Araki, N., Johnson, M. T., and Swanson, J. A. (1996). A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J. Cell Biol. 135, 1249-1260. doi: 10.1083/jcb.135.5.1249.
7. Asare, R., and Abu Kwaik, Y. (2010). Exploitation of host cell biology and evasion of immunity by francisella tularensis. Front. Microbiol. 1:145. doi: 10.3389/fmicb.2010.00145.
8. Atianand, M. K., Duffy, E. B., Shah, A., Kar, S., Malik, M., and Harton, J. A. (2011). Francisella tularensis reveals a disparity between human and mouse NLRP3 inflammasome activation. J. Biol. Chem. 286, 39033-39042. doi: 10.1074/jbc.M111.244079.
9. Becker, J. C., Andersen, M. H., Schrama, D., and Thor, S. P. (2013). Immune-suppressive properties of the tumor microenvironment. Cancer Immunol. Immunother. 62, 1137-1148. doi: 10.1007/s00262-013-1434-6.
10. Bosio, C. M. (2011). The subversion of the immune system by francisella tularensis. Front. Microbiol. 2:9. doi: 10.3389/fmicb.2011.00009.
11. Bosio, C. M., Bielefeldt-Ohmann, H., and Belisle, J. T. (2007). Active suppression of the pulmonary immune response by Francisella tularensis Schu4. J. Immunol. 178, 4538-4547.
12. Bourquin, C., Hotz, C., Noerenberg, D., Voelkl, A., Heidegger, S., Roetzer, L. C., et al. (2011). Systemic cancer therapy with a small molecule agonist of toll-like receptor 7 can be improved by circumventing TLR tolerance. Cancer Res. 71, 5123-5133. doi: 10.1158/0008-5472.CAN-10-3903.
13. Brown, J., Wang, H., Hajishengallis, G. N., and Martin, M. (2011). TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J. Dent. Res. 90, 417-427. doi: 10.1177/0022034510381264.
14. Broz, P., and Monack, D. M. (2011). Molecular mechanisms of inflammasome activation during microbial infections. Immunol. Rev. 243, 174-190. doi: 10.1111/j.1600-065X.2011.01041.x.
15. Broz, P., and Monack, D. M. (2013). Newly described pattern recognition receptors team up against intracellular pathogens. Nat. Rev. Immunol. 13, 551-565. doi: 10.1038/nri3479.
16. Butchar, J. P., Cremer, T. J., Clay, C. D., Gavrilin, M. A., Wewers, M. D., Marsh, C. B., et al. (2008). Microarray analysis of human monocytes infected with Francisella tularensis identifies new targets of host response subversion. PLoS ONE 3:e2924. doi: 10.1371/journal.pone.0002924.
17. Butchar, J. P., Mehta, P., Justiniano, S. E., Guenterberg, K. D., Kondadasula, S. V., Mo, X., et al. (2010). Reciprocal regulation of activating and inhibitory Fc{gamma} receptors by TLR7/8 activation: implications for tumor immunotherapy. Clin. Cancer Res. 16, 2065-2075. doi: 10.1158/1078-0432.CCR-09-2591.
18. Celli, J., and Zahrt, T. C. (2013). Mechanisms of Francisella tularensis intracellular pathogenesis. Cold Spring Harb. Perspect. Med. 3, a010314. doi: 10.1101/cshperspect.a010314.
19. Chase, J. C., and Bosio, C. M. (2010). The presence of CD14 overcomes evasion of innate immune responses by virulent Francisella tularensis in human dendritic cells in vitro and pulmonary cells in vivo. Infect. Immun. 78, 154-167. doi: 10.1128/IAI.00750-09.
20. Chase, J. C., Celli, J., and Bosio, C. M. (2009). Direct and indirect impairment of human dendritic cell function by virulent Francisella tularensis Schu S4. Infect. Immun. 77, 180-195. doi: 10.1128/IAI.00879-08.
21. Chen, M., Griffith, B. P., Lucia, H. L., and Hsiung, G. D. (1988). Efficacy of S26308 against guinea pig cytomegalovirus infection. Antimicrob. Agents Chemother. 32, 678-683. doi: 10.1128/AAC.32.5.678.
22. Chen, Q., Powell, D. W., Rane, M. J., Singh, S., Butt, W., Klein, J. B., et al. (2003). Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J. Immunol. 170, 5302-5308.
23. Chiu, H. C., Yang, J., Soni, S., Kulp, S. K., Gunn, J. S., Schlesinger, L. S., et al. (2009). Pharmacological exploitation of an off-target antibacterial effect of the cyclooxygenase-2 inhibitor celecoxib against Francisella tularensis. Antimicrob. Agents Chemother. 53, 2998-3002. doi: 10.1128/AAC.00048-09.
24. Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., and Gusovsky, F. (1999). Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J. Biol. Chem. 274, 10689-10692. doi: 10.1074/jbc.274.16.10689.
25. Clemens, D. L., and Horwitz, M. A. (2007). Uptake and intracellular fate of Francisella tularensis in human macrophages. Ann. N.Y. Acad. Sci. 1105, 160-186. doi: 10.1196/annals.1409.001.
26. Clynes, R. A., Towers, T. L., Presta, L. G., and Ravetch, J. V. (2000). Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat. Med. 6, 443-446. doi: 10.1038/74704.
27. Coley, W. B. (1891). II. Contribution to the knowledge of sarcoma. Ann. Surg. 14, 199-220. doi: 10.1097/00000658-189112000-00015.
28. Collazo, C. M., Sher, A., Meierovics, A. I., and Elkins, K. L. (2006). Myeloid differentiation factor-88 (MyD88) is essential for control of primary in vivo Francisella tularensis LVS infection, but not for control of intra-macrophage bacterial replication. Microbes Infect. 8, 779-790. doi: 10.1016/j.micinf.2005.09.014.
29. Conlan, J. W., Chen, W., Bosio, C. M., Cowley, S. C., and Elkins, K. L. (2011). Infection of mice with Francisella as an immunological model. Curr. Protoc. Immunol. Chapter 19, Unit 19.14. doi: 10.1002/0471142735.im1914s93.
30. Crane, D. D., Griffin, A. J., Wehrly, T. D., and Bosio, C. M. (2013). B1a cells enhance susceptibility to infection with virulent Francisella tularensis via modulation of NK/NKT cell responses. J. Immunol. 190, 2756-2766. doi: 10.4049/jimmunol.1202697.
31. Cremer, T. J., Butchar, J. P., and Tridandapani, S. (2011). Francisella subverts innate immune signaling: focus on PI3K/Akt. Front. Microbiol. 5:13. doi: 10.3389/fmicb.2011.00013.
32. Cremer, T. J., Ravneberg, D. H., Clay, C. D., Piper-Hunter, M. G., Marsh, C. B., Elton, T. S., et al. (2009). MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response. PLoS ONE 4:e8508. doi: 10.1371/journal.pone.0008508.
33. Dai, S., Rajaram, M. V., Curry, H. M., Leander, R., and Schlesinger, L. S. (2013). Fine tuning inflammation at the front door: macrophage complement receptor 3-mediates phagocytosis and immune suppression for Francisella tularensis. PLoS Pathog. 9:e1003114. doi: 10.1371/journal.ppat.1003114.
34. Damen, J. E., Liu, L., Rosten, P., Humphries, R. K., Jefferson, A. B., Majerus, P. W., et al. (1996). The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase. Proc. Natl. Acad. Sci. U.S.A. 93, 1689-1693. doi: 10.1073/pnas.93.4.1689.
35. Dotson, R. J., Rabadi, S. M., Westcott, E. L., Bradley, S., Catlett, S. V., Banik, S., et al. (2013). Repression of inflammasome by francisella tularensis during early stages of infection. J. Biol. Chem. 288, 23844-23857. doi: 10.1074/jbc.M113.490086.
36. Duenas, A. I., Aceves, M., Orduna, A., Diaz, R., Sanchez, C. M., and Garcia-Rodriguez, C. (2006). Francisella tularensis LPS induces the production of cytokines in human monocytes and signals via Toll-like receptor 4 with much lower potency than E. coli LPS. Int. Immunol. 18, 785-795. doi: 10.1093/intimm/dxl015.
37. Elkins, K. L., Cowley, S. C., and Bosio, C. M. (2007). Innate and adaptive immunity to Francisella. Ann. N.Y. Acad. Sci. 1105, 284-324. doi: 10.1196/annals.1409.014.
38. Eulalio, A., Schulte, L., and Vogel, J. (2012). The mammalian microRNA response to bacterial infections. RNA Biol. 9, 742-750. doi: 10.4161/rna.20018.
39. Fernandes-Alnemri, T., Yu, J. W., Juliana, C., Solorzano, L., Kang, S., Wu, J., et al. (2010). The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 11, 385-393. doi: 10.1038/ni.1859.
40. Gallois, A., Klein, J. R., Allen, L. A., Jones, B. D., and Nauseef, W. M. (2001). Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane. J. Immunol. 166, 5741-5748.
41. Gavrilin, M. A., Bouakl, I. J., Knatz, N. L., Duncan, M. D., Hall, M. W., Gunn, J. S., et al. (2006). Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release. Proc. Natl. Acad. Sci. U.S A. 103, 141-146. doi: 10.1073/pnas.0504271103.
42. Goldstein, D., Hertzog, P., Tomkinson, E., Couldwell, D., Mccarville, S., Parrish, S., et al. (1998). Administration of imiquimod, an interferon inducer, in asymptomatic human immunodeficiency virus-infected persons to determine safety and biologic response modification. J. Infect. Dis. 178, 858-861. doi: 10.1086/515343.
43. Greisman, S. E., and Hornick, R. B. (1975). The nature of endotoxin tolerance. Trans. Am. Clin. Climatol. Assoc. 86, 43-50.
44. Greisman, S. E., Hornick, R. B., Carozza, F. A. Jr., and Woodward, T. E. (1963). The role of endotoxin during typhoid fever and tularemia in man. I. Acquisition of tolerance to endotoxin. J. Clin. Invest. 42, 1064-1075. doi: 10.1172/JCI104792.
45. Hall, J. D., Woolard, M. D., Gunn, B. M., Craven, R. R., Taft-Benz, S., Frelinger, J. A., et al. (2008). Infected-host-cell repertoire and cellular response in the lung following inhalation of Francisella tularensis Schu S4, LVS, or U112. Infect. Immun. 76, 5843-5852. doi: 10.1128/IAI.01176-08.
46. Hart, O. M., Athie-Morales, V., O'Connor, G. M., and Gardiner, C. M. (2005). TLR7/8-mediated activation of human NK cells results in accessory cell-dependent IFN-gamma production. J. Immunol. 175, 1636-1642.
47. Hemmings, B. A., and Restuccia, D. F. (2012). PI3K-PKB/Akt pathway. Cold Spring Harb. Perspect. Biol. 4, a011189. doi: 10.1101/cshperspect.a011189.
48. Henry, T., Brotcke, A., Weiss, D. S., Thompson, L. J., and Monack, D. M. (2007). Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J. Exp. Med. 204, 987-994. doi: 10.1084/jem.20062665.
49. Hers, I., Vincent, E. E., and Tavare, J. M. (2011). Akt signalling in health and disease. Cell Signal. 23, 1515-1527. doi: 10.1016/j.cellsig.2011.05.004.
50. Hornung, V., Rothenfusser, S., Britsch, S., Krug, A., Jahrsdorfer, B., Giese, T., et al. (2002). Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168, 4531-4537.
51. Hoyal, C. R., Gutierrez, A., Young, B. M., Catz, S. D., Lin, J. H., Tsichlis, P. N., et al. (2003). Modulation of p47PHOX activity by site-specific phosphorylation: Akt-dependent activation of the NADPH oxidase. Proc. Natl. Acad. Sci. U.S.A. 100, 5130-5135. doi: 10.1073/pnas.1031526100.
52. Hrstka, R., Stulik, J., and Vojtesek, B. (2005). The role of MAPK signal pathways during Francisella tularensis LVS infection-induced apoptosis in murine macrophages. Microbes Infect. 7, 619-625. doi: 10.1016/j.micinf.2004.12.020.
53. Ireland, R., Olivares-Zavaleta, N., Warawa, J. M., Gherardini, F. C., Jarrett, C., Hinnebusch, B. J., et al. (2010). Effective, broad spectrum control of virulent bacterial infections using cationic DNA liposome complexes combined with bacterial antigens. PLoS Pathog. 6:e1000921. doi: 10.1371/journal.ppat.1000921.
54. Johansson, A., Celli, J., Conlan, W., Elkins, K. L., Forsman, M., Keim, P. S., et al. (2010). Objections to the transfer of Francisella novicida to the subspecies rank of Francisella tularensis. Int. J. Syst. Evol. Microbiol. 60(pt 8), 1717-1718. author reply: 1718-1720. doi: 10.1099/ijs.0.022830-0.
55. Jones, C. L., Napier, B. A., Sampson, T. R., Llewellyn, A. C., Schroeder, M. R., and Weiss, D. S. (2012). Subversion of host recognition and defense systems by Francisella spp. Microbiol. Mol. Biol. Rev. 76, 383-404. doi: 10.1128/MMBR.05027-11.
56. Jones, J. W., Kayagaki, N., Broz, P., Henry, T., Newton, K., O'Rourke, K., et al. (2010). Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc. Natl. Acad. Sci. U.S A. 107, 9771-9776. doi: 10.1073/pnas.1003738107.
57. Katz, J., Zhang, P., Martin, M., Vogel, S. N., and Michalek, S. M. (2006). Toll-like receptor 2 is required for inflammatory responses to Francisella tularensis LVS. Infect. Immun. 74, 2809-2816. doi: 10.1128/IAI.74.5.2809-2816.2006.
58. Keates, S., Sougioultzis, S., Keates, A. C., Zhao, D., Peek, R. M. Jr., Shaw, L. M., et al. (2001). cag+ Helicobacter pylori induce transactivation of the epidermal growth factor receptor in AGS gastric epithelial cells. J. Biol. Chem. 276, 48127-48134. doi: 10.1074/jbc.M107630200.
59. Kushner, E. J., and Bautch, V. L. (2013). Building blood vessels in development and disease. Curr. Opin. Hematol. 20, 231-236. doi: 10.1097/MOH.0b013e328360614b.
60. Leavy, O. (2012). Tumour immunology: a close-range dual hit for tumour immunity. Nat. Rev. Immunol. 12, 227. doi: 10.1038/nri3189.
61. Lembo, A., Pelletier, M., Iyer, R., Timko, M., Dudda, J. C., West, T. E., et al. (2008). Administration of a synthetic TLR4 agonist protects mice from pneumonic tularemia. J. Immunol. 180, 7574-7581.
62. Lindgren, H., Stenman, L., Tarnvik, A., and Sjostedt, A. (2005). The contribution of reactive nitrogen and oxygen species to the killing of Francisella tularensis LVS by murine macrophages. Microbes Infect. 7, 467-475. doi: 10.1016/j.micinf.2004.11.020.
63. Lu, H., Dietsch, G. N., Matthews, M. A., Yang, Y., Ghanekar, S., Inokuma, M., et al. (2012). VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin. Cancer Res. 18, 499-509. doi: 10.1158/1078-0432.CCR-11-1625.
64. Mailman, T. L., and Schmidt, M. H. (2005). Francisella philomiragia adenitis and pulmonary nodules in a child with chronic granulomatous disease. Can. J. Infect. Dis. Med. Microbiol. 16, 245-248.
65. Malik, M., Bakshi, C. S., Sahay, B., Shah, A., Lotz, S. A., and Sellati, T. J. (2006). Toll-like receptor 2 is required for control of pulmonary infection with Francisella tularensis. Infect. Immun. 74, 3657-3662. doi: 10.1128/IAI.02030-05.
66. Mansell, A., Khelef, N., Cossart, P., and O'Neill, L. A. (2001). Internalin B activates nuclear factor-kappa B via Ras, phosphoinositide 3-kinase, and Akt. J. Biol. Chem. 276, 43597-43603. doi: 10.1074/jbc.M105202200.
67. Mantia, L. L., Vacchi, L., Rovaris, M., Di Pietrantonj, C., Ebers, G., Fredrikson, S., et al. (2013). Interferon beta for secondary progressive multiple sclerosis: a systematic review. J. Neurol Neurosurg. Psychiatry 84, 420-426. doi: 10.1136/jnnp-2012-303291.
68. Mariathasan, S., Weiss, D. S., Dixit, V. M., and Monack, D. M. (2005). Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. J. Exp. Med. 202, 1043-1049. doi: 10.1084/jem.20050977.
69. Mccaffrey, R. L., and Allen, L. A. (2006). Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. J. Leukoc. Biol. 80, 1224-1230. doi: 10.1189/jlb.0406287.
70. Mccaffrey, R. L., Schwartz, J. T., Lindemann, S. R., Moreland, J. G., Buchan, B. W., Jones, B. D., et al. (2010). Multiple mechanisms of NADPH oxidase inhibition by type A and type B Francisella tularensis. J. Leukoc. Biol. 88, 791-805. doi: 10.1189/jlb.1209811.
71. Medina, E. A., Morris, I. R., and Berton, M. T. (2010). Phosphatidylinositol 3-kinase activation attenuates the TLR2-mediated macrophage proinflammatory cytokine response to Francisella tularensis live vaccine strain. J. Immunol. 185, 7562-7572. doi: 10.4049/jimmunol.0903790.
72. Melillo, A. A., Bakshi, C. S., and Melendez, J. A. (2010). Francisella tularensis antioxidants harness reactive oxygen species to restrict macrophage signaling and cytokine production. J. Biol. Chem. 285, 27553-27560. doi: 10.1074/jbc.M110.144394.
73. Melillo, A. A., Mahawar, M., Sellati, T. J., Malik, M., Metzger, D. W., Melendez, J. A., et al. (2009). Identification of Francisella tularensis live vaccine strain CuZn superoxide dismutase as critical for resistance to extracellularly generated reactive oxygen species. J. Bacteriol. 191, 6447-6456. doi: 10.1128/JB.00534-09.
74. Mohapatra, N. P., Soni, S., Rajaram, M. V., Dang, P. M., Reilly, T. J., El Benna, J., et al. (2010). Francisella acid phosphatases inactivate the NADPH oxidase in human phagocytes. J. Immunol. 184, 5141-5150. doi: 10.4049/jimmunol.0903413.
75. Mohapatra, N. P., Soni, S., Rajaram, M. V., Strandberg, K. L., and Gunn, J. S. (2013). Type A Francisella tularensis acid phosphatases contribute to pathogenesis. PLoS ONE 8:e56834. doi: 10.1371/journal.pone.0056834.
76. Morris, M., and Li, L. (2012). Molecular mechanisms and pathological consequences of endotoxin tolerance and priming. Arch. Immunol. Ther. Exp. (Warsz) 60, 13-18. doi: 10.1007/s00005-011-0155-9.
77. Moser, B., and Loetscher, P. (2001). Lymphocyte traffic control by chemokines. Nat. Immunol. 2, 123-128. doi: 10.1038/84219.
78. Nylund, A., Ottem, K. F., Watanabe, K., Karlsbakk, E., and Krossoy, B. (2006). Francisella sp. (Family Francisellaceae) causing mortality in Norwegian cod (Gadus morhua) farming. Arch. Microbiol. 185, 383-392. doi: 10.1007/s00203-006-0109-5.
79. Park, S. W., Kim, H. S., Hah, J. W., Jeong, W. J., Kim, K. H., and Sung, M. W. (2010). Celecoxib inhibits cell proliferation through the activation of ERK and p38 MAPK in head and neck squamous cell carcinoma cell lines. Anticancer Drugs 21, 823-830. doi: 10.1097/CAD.0b013e32833dada8.
80. Parsa, K. V., Butchar, J. P., Rajaram, M. V., Cremer, T. J., Gunn, J. S., Schlesinger, L. S., et al. (2008a). Francisella gains a survival advantage within mononuclear phagocytes by suppressing the host IFNgamma response. Mol. Immunol. 45, 3428-3437. doi: 10.1016/j.molimm.2008.04.006.
81. Parsa, K. V., Butchar, J. P., Rajaram, M. V., Cremer, T. J., and Tridandapani, S. (2008b). The tyrosine kinase Syk promotes phagocytosis of Francisella through the activation of Erk. Mol. Immunol. 45, 3012-3021. doi: 10.1016/j.molimm.2008.01.011.
82. Parsa, K. V., Ganesan, L. P., Rajaram, M. V., Gavrilin, M. A., Balagopal, A., Mohapatra, N. P., et al. (2006). Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP. PLoS Pathog. 2:e71. doi: 10.1371/journal.ppat.0020071.
83. Petiot, A., Ogier-Denis, E., Blommaart, E. F., Meijer, A. J., and Codogno, P. (2000). Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J. Biol. Chem. 275, 992-998. doi: 10.1074/jbc.275.2.992.
84. Phillips, N. J., Schilling, B., Mclendon, M. K., Apicella, M. A., and Gibson, B. W. (2004). Novel modification of lipid A of Francisella tularensis. Infect. Immun. 72, 5340-5348. doi: 10.1128/IAI.72.9.5340-5348.2004.
85. Pockros, P. J., Guyader, D., Patton, H., Tong, M. J., Wright, T., Mchutchison, J. G., et al. (2007). Oral resiquimod in chronic HCV infection: safety and efficacy in 2 placebo-controlled, double-blind phase IIa studies. J. Hepatol. 47, 174-182. doi: 10.1016/j.jhep.2007.02.025.
86. Polsinelli, T., Meltzer, M. S., and Fortier, A. H. (1994). Nitric oxide-independent killing of Francisella tularensis by IFN-gamma-stimulated murine alveolar macrophages. J. Immunol. 153, 1238-1245.
87. Qin, A., and Mann, B. J. (2006). Identification of transposon insertion mutants of Francisella tularensis tularensis strain Schu S4 deficient in intracellular replication in the hepatic cell line HepG2. BMC Microbiol. 6:69. doi: 10.1186/1471-2180-6-69.
88. Qin, A., Scott, D. W., Rabideau, M. M., Moore, E. A., and Mann, B. J. (2011). Requirement of the CXXC motif of novel Francisella infectivity potentiator protein B FipB, and FipA in virulence of F. tularensis subsp. tularensis. PLoS ONE 6:e24611. doi: 10.1371/journal.pone.0024611.
89. Qureshi, S. T., Lariviere, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P., et al. (1999). Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J. Exp. Med. 189, 615-625. doi: 10.1084/jem.189.4.615.
90. Rajaram, M. V., Ganesan, L. P., Parsa, K. V., Butchar, J. P., Gunn, J. S., and Tridandapani, S. (2006). Akt/Protein kinase B modulates macrophage inflammatory response to Francisella infection and confers a survival advantage in mice. J. Immunol. 177, 6317-6324.
91. Rathinam, V. A., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., et al. (2010). The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395-402. doi: 10.1038/ni.1864.
92. Rick, L. C., and Wu, T. H. (2007). Animal models of Francisella tularensis infection. Ann. N.Y. Acad. Sci. 1105, 238-265. doi: 10.1196/annals.1409.003.
93. Sakai, K., Suzuki, H., Oda, H., Akaike, T., Azuma, Y., Murakami, T., et al. (2006). Phosphoinositide 3-kinase in nitric oxide synthesis in macrophage: critical dimerization of inducible nitric-oxide synthase. J. Biol. Chem. 281, 17736-17742. doi: 10.1074/jbc.M601896200.
94. Sandstrom, G., Tarnvik, A., and Wolf-Watz, H. (1987). Immunospecific T-lymphocyte stimulation by membrane proteins from Francisella tularensis. J. Clin. Microbiol. 25, 641-644.
95. Santic, M., Molmeret, M., and Abu, K. Y. (2005). Modulation of biogenesis of the Francisella tularensis subsp. novicida-containing phagosome in quiescent human macrophages and its maturation into a phagolysosome upon activation by IFN-gamma. Cell Microbiol. 7, 957-967. doi: 10.1111/j.1462-5822.2005.00529.x.
96. Savva, A., and Roger, T. (2013). Targeting toll-like receptors: promising therapeutic strategies for the management of sepsis-associated pathology and infectious diseases. Front. Immunol. 4:387. doi: 10.3389/fimmu.2013.00387.
97. Schmid, G. P., Catino, D., Suffin, S. C., Martone, W. J., and Kaufmann, A. F. (1983). Granulomatous pleuritis caused by Francisella tularensis: possible confusion with tuberculous pleuritis. Am. Rev. Respir. Dis. 128, 314-316.
98. Seger, R. A., Hollis, D. G., Weaver, R. E., and Hitzig, W. H. (1982). Chronic granulomatous disease: fatal septicemia caused by an unnamed gram-negative bacterium. J. Clin. Microbiol. 16, 821-825.
99. Shaw, G. M., Levy, P. C., and Lobuglio, A. F. (1978). Human monocyte cytotoxicity to tumor cells. I. Antibody-dependent cytotoxicity. J. Immunol. 121, 573-578.
100. Sjostedt, A. (2003). Virulence determinants and protective antigens of Francisella tularensis. Curr. Opin. Microbiol. 6, 66-71. doi: 10.1016/S1369-5274(03)00002-X.
101. Sjostedt, A. (2007). Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann. N.Y. Acad. Sci. 1105, 1-29. doi: 10.1196/annals.1409.009.
102. Sjostedt, A., Sandstrom, G., Tarnvik, A., and Jaurin, B. (1989). Molecular cloning and expression of a T-cell stimulating membrane protein of Francisella tularensis. Microb. Pathog. 6, 403-414. doi: 10.1016/0882-4010(89)90082-X.
103. Sjostedt, A., Tarnvik, A., and Sandstrom, G. (1991). The T-cell-stimulating 17-kilodalton protein of Francisella tularensis LVS is a lipoprotein. Infect. Immun. 59, 3163-3168.
104. Sliwkowski, M. X., Lofgren, J. A., Lewis, G. D., Hotaling, T. E., Fendly, B. M., and Fox, J. A. (1999). Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin. Oncol. 26, 60-70.
105. Spiegel, R. J. (1985). INTRON A (interferon alfa-2b): clinical overview. Cancer Treat. Rev. 12(Suppl. B), 5-16.
106. Stenmark, S., Lindgren, H., Tarnvik, A., and Sjostedt, A. (2003). Specific antibodies contribute to the host protection against strains of Francisella tularensis subspecies holarctica. Microb. Pathog. 35, 73-80. doi: 10.1016/S0882-4010(03)00095-0.
107. Stenmark, S., and Sjostedt, A. (2004). Transfer of specific antibodies results in increased expression of TNF-alpha and IL12 and recruitment of neutrophils to the site of a cutaneous Francisella tularensis infection. J. Med. Microbiol. 53, 501-504. doi: 10.1099/jmm.0.05352-0.
108. Stenmark, S., Sunnemark, D., Bucht, A., and Sjostedt, A. (1999). Rapid local expression of interleukin-12, tumor necrosis factor alpha, and gamma interferon after cutaneous Francisella tularensis infection in tularemia-immune mice. Infect. Immun. 67, 1789-1797.
109. Stephenson, R. M., Lim, C. M., Matthews, M., Dietsch, G., Hershberg, R., and Ferris, R. L. (2013). TLR8 stimulation enhances cetuximab-mediated natural killer cell lysis of head and neck cancer cells and dendritic cell cross-priming of EGFR-specific CD8(+) T cells. Cancer Immunol. Immunother. 62, 1347-1357. doi: 10.1007/s00262-013-1437-3.
110. Telepnev, M., Golovliov, I., Grundstrom, T., Tarnvik, A., and Sjostedt, A. (2003). Francisella tularensis inhibits Toll-like receptor-mediated activation of intracellular signalling and secretion of TNF-alpha and IL-1 from murine macrophages. Cell Microbiol. 5, 41-51. doi: 10.1046/j.1462-5822.2003.00251.x.
111. Telepnev, M., Golovliov, I., and Sjostedt, A. (2005). Francisella tularensis LVS initially activates but subsequently down-regulates intracellular signaling and cytokine secretion in mouse monocytic and human peripheral blood mononuclear cells. Microb. Pathog. 38, 239-247. doi: 10.1016/j.micpath.2005.02.003.
112. Thakran, S., Li, H., Lavine, C. L., Miller, M. A., Bina, J. E., Bina, X. R., et al. (2008). Identification of Francisella tularensis lipoproteins that stimulate the toll-like receptor (TLR) 2/TLR1 heterodimer. J. Biol. Chem. 283, 3751-3760. doi: 10.1074/jbc.M706854200.
113. Todd, P. A., and Goa, K. L. (1992). Interferon gamma-1b. A review of its pharmacology and therapeutic potential in chronic granulomatous disease. Drugs 43, 111-122. doi: 10.2165/00003495-199243010-00008.
114. Tomai, M. A., Gibson, S. J., Imbertson, L. M., Miller, R. L., Myhre, P. E., Reiter, M. J., et al. (1995). Immunomodulating and antiviral activities of the imidazoquinoline S-28463. Antiviral Res. 28, 253-264. doi: 10.1016/0166-3542(95)00054-P.
115. Vacchelli, E., Eggermont, A., Sautes-Fridman, C., Galon, J., Zitvogel, L., Kroemer, G., et al. (2013). Trial Watch: toll-like receptor agonists for cancer therapy. Oncoimmunology 2, e25238. doi: 10.4161/onci.25238.
116. Vincent, K. J., and Zurini, M. (2012). Current strategies in antibody engineering: Fc engineering and pH-dependent antigen binding, bispecific antibodies and antibody drug conjugates. Biotechnol. J. 7, 1444-1450. doi: 10.1002/biot.201200250.
117. Waller, E. K. (2007). The role of sargramostim (rhGM-CSF) as immunotherapy. Oncologist 12(Suppl. 2), 22-26. doi: 10.1634/theoncologist.12-S2-22.
118. Weigel, B. J., Cooley, S., Defor, T., Weisdorf, D. J., Panoskaltsis-Mortari, A., Chen, W., et al. (2012). Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies. Am. J. Hematol. 87, 953-956. doi: 10.1002/ajh.23280.
119. Welsh, R. M., Bahl, K., Marshall, H. D., and Urban, S. L. (2012). Type 1 interferons and antiviral CD8 T-cell responses. PLoS Pathog. 8:e1002352. doi: 10.1371/journal.ppat.1002352.
120. West, M. A., and Heagy, W. (2002). Endotoxin tolerance: a review. Crit. Care Med. 30, S64-S73. doi: 10.1097/00003246-200201001-00009.
121. Whipp, M. J., Davis, J. M., Lum, G., De Boer, J., Zhou, Y., Bearden, S. W., et al. (2003). Characterization of a novicida-like subspecies of Francisella tularensis isolated in Australia. J. Med. Microbiol. 52, 839-842. doi: 10.1099/jmm.0.05245-0.
122. Wickstrum, J. R., Bokhari, S. M., Fischer, J. L., Pinson, D. M., Yeh, H. W., Horvat, R. T., et al. (2009). Francisella tularensis induces extensive caspase-3 activation and apoptotic cell death in the tissues of infected mice. Infect. Immun. 77, 4827-4836. doi: 10.1128/IAI.00246-09.
123. Williams, M. A., White, S. A., Miller, J. J., Toner, C., Withington, S., Newland, A. C., et al. (1998). Granulocyte-macrophage colony-stimulating factor induces activation and restores respiratory burst activity in monocytes from septic patients. J. Infect. Dis. 177, 107-115. doi: 10.1086/513802.
124. Witt, P. L., Ritch, P. S., Reding, D., Mcauliffe, T. L., Westrick, L., Grossberg, S. E., et al. (1993). Phase I trial of an oral immunomodulator and interferon inducer in cancer patients. Cancer Res. 53, 5176-5180.