Macrophage form, function, and phenotype in mycobacterial infection: Lessons from tuberculosis and other diseases

Pathogens and Disease

Volumn 74, Issue 7, 2016, Pages

  McClean, Colleen M ^a,b   Tobin, David M ^a,b  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Granuloma; Macrophage; Mycobacteria; Tuberculosis

Indexed keywords

CHOLESTEROL; CYTOKINE;

ATHEROSCLEROSIS; CELL FUNCTION; CELL STRUCTURE; CYTOKINE PRODUCTION; DISEASE COURSE; GRANULOMA; HUMAN; HYPOXIA; MACROPHAGE; MACROPHAGE ACTIVATION; MYCOBACTERIOSIS; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; SHORT SURVEY; TUBERCULOSIS; ANIMAL; IMMUNOLOGY; LIPID METABOLISM; METABOLISM; MICROBIOLOGY; MONONUCLEAR PHAGOCYTE; MYCOBACTERIUM TUBERCULOSIS; NEUTROPHIL CHEMOTAXIS; PATHOLOGY; PHAGOCYTOSIS; PHYSIOLOGY;

ANIMALS; CHEMOTAXIS, LEUKOCYTE; GRANULOMA; HUMANS; LIPID METABOLISM; MACROPHAGES; MONONUCLEAR PHAGOCYTE SYSTEM; MYCOBACTERIUM TUBERCULOSIS; PHAGOCYTOSIS; PHENOTYPE; TUBERCULOSIS;

EID: 85015348486     PISSN: None     EISSN: 2049632X     Source Type: Journal    
DOI: 10.1093/femspd/ftw068     Document Type: Short Survey

References (203)

1. Adams DO. The structure of mononuclear phagocytes differentiating in vivo. I. Sequential fine and histologic studies of the effect of Bacillus Calmette-Guerin (BCG). Am J Pathol 1974;76:17-48.
2. Aguilar-Ruiz SR, Torres-Aguilar H, Gonzalez-Dominguez E et al. Human CD16+ and CD16- monocyte subsets display unique effector properties in inflammatory conditions in vivo. J Leukocyte Biol 2011;90:1119-31.
3. Alatas F, Alatas O, Metintas M et al. Vascular endothelial growth factor levels in active pulmonary tuberculosis. Chest 2004;125:2156-9.
4. Alliot F, Godin I, Pessac B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res 1999;117:145-52.
5. Averill LE, Meagher RC, Gerrity RG. Enhanced monocyte progenitor cell proliferation in bone marrow of hyperlipemic swine. Am J Pathol 1989;135:369-77.
6. Avraham R, Haseley N, Brown D et al. Pathogen cell-to-cell variability drives heterogeneity in host immune responses. Cell 2015;162:1309-21.
7. Bafica A, Scanga CA, Serhan C et al. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenasedependent lipoxin production. J Clin Invest 2005;115:1601-6.
8. Bain CC, Bravo-Blas A, Scott CL et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 2014;15:929-37.
9. Balboa L, Romero MM, Basile JI et al. Paradoxical role of CD16+CCR2+CCR5+ monocytes in tuberculosis: efficient APC in pleural effusion but also mark disease severity in blood. J Leukocyte Biol 2011;90:69-75.
10. Baldan A, Gomes AV, Ping P et al. Loss of ABCG1 results in chronic pulmonary inflammation. J Immunol 2008;180:3560-8.
11. Barry CE, 3rd, Boshoff HI, Dartois V et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 2009;7:845-55.
12. Beamer GL, Flaherty DK, Assogba BD et al. Interleukin-10 promotes Mycobacterium tuberculosis disease progression in CBA/J mice. J Immunol 2008;181:5545-50.
13. Behar SM, DivangahiM, Remold HG. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? Nat Rev Microbiol 2010;8:668-74.
14. Biswas SK, Sica A, Lewis CE. Plasticity of macrophage function during tumor progression: regulation by distinct molecular mechanisms. J Immunol 2008;180:2011-7.
15. Briken V, Ahlbrand SE, Shah S. Mycobacterium tuberculosis and the host cell inflammasome: a complex relationship. Front Cell Infect Microbiol 2013;3:62.
16. Bustamante J, Boisson-Dupuis S, Abel L et al. Mendelian susceptibility tomycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-gamma immunity. Semin Immunol 2014;26:454-70.
17. Caceres N, Tapia G, Ojanguren I et al. Evolution of foamy macrophages in the pulmonary granulomas of experimental tuberculosis models. Tuberculosis 2009;89:175-82.
18. Cadena AM, Flynn JL, Fortune SM. The importance of first impressions: early events inmycobacterium tuberculosis infection influence outcome. mBio 2016;7:e00342-16.
19. Cambier CJ, Takaki KK, Larson RP et al. Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature 2014;505:218-22.
20. Capuano SV, 3rd, Croix DA, Pawar S et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infect Immun 2003;71:5831-44.
21. Chambers TJ, Spector WG. Inflammatory giant cells. Immunobiology 1982;161:283-9.
22. Chen M, Divangahi M, Gan H et al. Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J Exp Med 2008;205:2791-801.
23. Chensue SW, Terebuh PD, Warmington KS et al. Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function. J Immunol 1992;148:900-6.
24. Chinetti-Gbaguidi G, Baron M, Bouhlel MA et al. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARgamma and LXRalpha pathways. Circ Res 2011;108:985-95.
25. Cilfone NA, Perry CR, Kirschner DE et al. Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection. PloS One 2013;8:e68680.
26. Clay H, Volkman HE, Ramakrishnan L. Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity 2008;29:283-94.
27. Cooper AM, Khader SA. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev 2008;226:191-204.
28. Cooper AM, Kipnis A, Turner J et al. Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. J Immunol 2002;168:1322-7.
29. Cosma CL, Sherman DR, Ramakrishnan L. The secret lives of the pathogenic mycobacteria. Annu Rev Microbiol 2003;57: 641-76.
30. Cuchel M, Rader DJ. Macrophage reverse cholesterol transport: key to the regression of atherosclerosis? Circulation 2006;113:2548-55.
31. Cummings TJ, Hulette CM, Bigner SH et al. Ham56- immunoreactive macrophages in untreated infiltrating gliomas. Arch Pathol Lab Med 2001;125:637-41.
32. Cyktor JC, Carruthers B, Kominsky RA et al. IL-10 inhibits mature fibrotic granuloma formation during Mycobacterium tuberculosis infection. J Immunol 2013;190:2778-90.
33. Dallenga T, Schaible UE. Neutrophils in tuberculosis-first line of defence or booster of disease and targets for host-directed therapy? Pathog Dis 2016;74, DOI: 10.1093/femspd/ftw012.
34. Datta M, Via LE, Kamoun WS et al. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. P Natl Acad Sci USA 2015;112:1827-32.
35. D'Avila H, Maya-Monteiro CM, Bozza PT. Lipid bodies in innate immune response to bacterial and parasite infections. Int Immunopharmacol 2008;8:1308-15.
36. D'Avila H, Melo RC, Parreira GG et al. Mycobacterium bovis bacillus Calmette-Guerin induces TLR2-mediated formation of lipid bodies: intracellular domains for eicosanoid synthesis in vivo. J Immunol 2006;176:3087-97.
37. Davis JM, Clay H, Lewis JL et al. Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity 2002;17:693-702.
38. Davis JM, Ramakrishnan L. The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell 2009;136:37-49.
39. DeFife KM, Jenney CR, McNally AK et al. Interleukin-13 induces human monocyte/macrophage fusion and macrophage mannose receptor expression. J Immunol 1997;158:3385-90.
40. Divangahi M, Desjardins D, Nunes-Alves C et al. Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis. Nat Immunol 2010;11:751-8.
41. du Plessis N, Loebenberg L, Kriel M et al. Increased frequency of myeloid-derived suppressor cells during active tuberculosis and after recent mycobacterium tuberculosis infection suppresses T-cell function. AM J Resp Crit Care 2013;188: 724-32.
42. Duell BL, Tan CK, Carey AJ et al. Recent insights into microbial triggers of interleukin-10 production in the host and the impact on infectious disease pathogenesis. FEMS Immunol Med Mic 2012;64:295-313.
43. Duewell P, Kono H, Rayner KJ et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010;464:1357-61.
44. Duque-Correa MA, Kuhl AA, Rodriguez PC et al. Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas. P Natl Acad Sci USA 2014;111:E4024-32.
45. Ehlers S, Schaible UE. The granuloma in tuberculosis: dynamics of a host-pathogen collusion. Front Immunol 2012;3:411.
46. Epstein WL, Fukuyama K, Danno K et al. Granulomatous inflammation in normal and athymic mice infected with schistosoma mansoni: an ultrastructural study. J Pathol 1979;127:207-15.
47. Erwig LP, Kluth DC,Walsh GM et al. Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines. J Immunol 1998;161:1983-8.
48. Eum SY, Kong JH, Hong MS et al. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB. Chest 2010;137:122-8.
49. Feldman DL, Mogelesky TC, Liptak BF et al. Leukocytosis in rabbits with diet-induced atherosclerosis. Arterioscler Thromb 1991;11:985-94.
50. Feng B, Yao PM, Li Y et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 2003;5:781-92.
51. Feng CG, Jankovic D, Kullberg M et al. Maintenance of pulmonary Th1 effector function in chronic tuberculosis requires persistent IL-12 production. J Immunol 2005;174:4185-92.
52. Feng CG, Kaviratne M, Rothfuchs AG et al. NK cell-derived IFNgamma differentially regulates innate resistance and neutrophil response in T cell-deficient hosts infected with Mycobacterium tuberculosis. J Immunol 2006;177:7086-93.
53. Feng Y, Dorhoi A, Mollenkopf HJ et al. Platelets direct monocyte differentiation into epithelioid-like multinucleated giant foam cells with suppressive capacity uponmycobacterial stimulation. J Infect Dis 2014;210:1700-10.
54. Flynn JL, Goldstein MM, Chan J et al. Tumor necrosis factoralpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 1995;2: 561-72.
55. Frankenberger M, Sternsdorf T, Pechumer H et al. Differential cytokine expression in human blood monocyte subpopulations: a polymerase chain reaction analysis. Blood 1996;87:373-7.
56. Frieden TR, Sterling TR, Munsiff SS et al. Tuberculosis. Lancet 2003;362:887-99.
57. Galagan JE, Minch K, Peterson M et al. The Mycobacterium tuberculosis regulatory network and hypoxia. Nature 2013;499: 178-83.
58. Gallardo-Soler A, Gomez-Nieto C, Campo ML et al. Arginase I induction by modified lipoproteins in macrophages: a peroxisome proliferator-activated receptor-gamma/delta-mediated effect that links lipid metabolism and immunity. Mol Endocrinol 2008;22:1394-402.
59. Gautier EL, Shay T, Miller J et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity ofmouse tissue macrophages. Nat Immunol 2012;13:1118-28.
60. Gideon HP, Flynn JL. Latent tuberculosis: what the host "sees"? Immunol Res 2011;50:202-12.
61. Gideon HP, Phuah J, Myers AJ et al. Variability in tuberculosis granuloma T cell responses exists, but a balance of pro- and anti-inflammatory cytokines is associated with sterilization. PLoS Pathog 2015;11:e1004603.
62. Ginhoux F, Greter M, Leboeuf M et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010;330:841-5.
63. Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 2014;14:392-404.
64. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003;3:23-35.
65. Gordon S, Pluddemann A, Martinez Estrada F. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev 2014;262:36-55.
66. Guilliams M, De Kleer I, Henri S et al. Alveolar macrophages develop from fetal monocytes that differentiate into longlived cells in the first week of life via GM-CSF. J Exp Med 2013;210:1977-92.
67. Guirado E, Schlesinger LS, Kaplan G. Macrophages in tuberculosis: friend or foe. Semin Immunopathol 2013;35: 563-83.
68. Harris K, Chalhoub M, Maroun R et al. Lipoid pneumonia: a challenging diagnosis. Heart Lung 2011;40:580-4.
69. Hashimoto D, Chow A, Noizat C et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 2013;38:792-804.
70. Helming L, Gordon S. Macrophage fusion induced by IL-4 alternative activation is a multistage process involving multiple target molecules. Eur J Immunol 2007a;37:33-42.
71. Helming L, Gordon S. Themolecular basis of macrophage fusion. Immunobiology 2007b;212:785-93.
72. Henderson RA, Watkins SC, Flynn JL. Activation of human dendritic cells following infection with Mycobacterium tuberculosis. J Immunol 1997;159:635-43.
73. Herbomel P, Thisse B, Thisse C. Ontogeny and behaviour of early macrophages in the zebrafish embryo. Development 1999;126:3735-45.
74. Hernandez-Pando R, Orozcoe H, Sampieri A et al. Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis. Immunology 1996;89:26-33.
75. Hettinger J, Richards DM, Hansson J et al. Origin of monocytes and macrophages in a committed progenitor. Nat Immunol 2013;14:821-30.
76. Higgins DM, Sanchez-Campillo J, Rosas-Taraco AG et al. Lack of IL-10 alters inflammatory and immune responses during pulmonary Mycobacterium tuberculosis infection. Tuberculosis 2009;89:149-57.
77. Hoeffel G, Wang Y, Greter M et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med 2012;209:1167-81.
78. Huang Z, Luo Q, Guo Y et al. Mycobacterium tuberculosisinduced polarization of human macrophage orchestrates the formation and development of Tuberculous Granulomas in vitro. PloS One 2015;10:e0129744.
79. Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissuespecific context. Nat Rev Immunol 2014;14:81-93.
80. Ihling C, Gobel HR, Lippoldt A et al. Endothelin-1-like immunoreactivity in human atherosclerotic coronary tissue: a detailed analysis of the cellular distribution of endothelin-1. J Pathol 1996;179:303-8.
81. Ivashkiv LB. Epigenetic regulation of macrophage polarization and function. Trends Immunol 2013;34:216-23.
82. Jakubzick C, Gautier EL, Gibbings SL et al. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 2013;39:599-610.
83. James DG. A clinicopathological classification of granulomatous disorders. Postgrad Med J 2000;76:457-65.
84. Junqueira-Kipnis AP, Kipnis A, Jamieson A et al. NK cells respond to pulmonary infection with Mycobacterium tuberculosis, but play aminimal role in protection. J Immunol 2003;171: 6039-45.
85. Kahnert A, Seiler P, Stein M et al. Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis. Eur J Immunol 2006;36:631-47.
86. Kalayoglu MV, Byrne GI. Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis 1998;177:725-9.
87. Keane J, Balcewicz-Sablinska MK, Remold HG et al. Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect Immun 1997;65:298-304.
88. Khader SA, Pearl JE, Sakamoto K et al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol 2005;175:788-95.
89. Knaul JK, Jorg S, Oberbeck-Mueller D et al. Lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis. AM J Resp Crit Care 2014;190:1053-66.
90. Kondo E, Kanai K. Accumulation of cholesterol esters in macrophages incubated with mycobacteria in vitro. Jpn J Med Sci Biol 1976;29:123-37.
91. Kopf M, Schneider C, Nobs SP. The development and function of lung-resident macrophages and dendritic cells. Nat Immunol 2015;16:36-44.
92. Kumar A, Deshane JS, Crossman DK et al. Heme oxygenase-1- derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon. J Biol Chem 2008;283:18032-9.
93. Kunjathoor VV, Febbraio M, Podrez EA et al. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem 2002;277:49982-8.
94. Kupz A, Zedler U, StaberMet al. ESAT-6-dependent cytosolic pattern recognition drives noncognate tuberculosis control in vivo. J Clin Invest 2016;126:2109-22.
95. Kzhyshkowska J, Neyen C, Gordon S. Role of macrophage scavenger receptors in atherosclerosis. Immunobiology 2012;217:492-502.
96. Laoui D, Van Overmeire E, Di Conza G et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res 2014;74:24-30.
97. Lastrucci C, Benard A, Balboa L et al. Tuberculosis is associated with expansion of amotile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis. Cell Res 2015;25:1333-51.
98. Lavin Y, Winter D, Blecher-Gonen R et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 2014;159:1312-26.
99. Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 2011;11:750-61.
100. Lay G, Poquet Y, Salek-Peyron P et al. Langhans giant cells from M. tuberculosis-induced human granulomas cannot mediate mycobacterial uptake. J Pathol 2007;211:76-85.
101. Ley K, Miller YI, Hedrick CC. Monocyte and macrophage dynamics during atherogenesis. Arterioscl Throm Vas Biol 2011;31:1506-16.
102. Li J, Pritchard DK,Wang X et al. cDNAmicroarray analysis reveals fundamental differences in the expression profiles of primary human monocytes, monocyte-derived macrophages, and alveolar macrophages. J Leukocyte Biol 2007;81:328-35.
103. Lin EY, Pollard JW. Tumor-associated macrophages press the angiogenic switch in breast cancer. Cancer Res 2007;67:5064-6.
104. Lin PL, Ford CB, Coleman MT et al. Sterilization of granulomas is common in active and latent tuberculosis despite withinhost variability in bacterial killing. Nat Med 2014;20:75-9.
105. Lockhart E, Green AM, Flynn JL. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol 2006;177:4662-9.
106. Lugo-Villarino G, Neyrolles O. Manipulation of the mononuclear phagocyte system by Mycobacterium tuberculosis. Cold Spring Harbor Perspect Med 2014;4:a018549.
107. Mahajan S, Dkhar HK, Chandra V et al. Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPARgamma and TR4 for survival. J Immunol 2012;188: 5593-603.
108. Marakalala MJ, Raju RM, Sharma K et al. Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat Med 2016;22:531-8.
109. Marino S, Cilfone NA, Mattila JT et al. Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection. Infect Immun 2015;83:324-38.
110. Marino S, Pawar S, Fuller CL et al. Dendritic cell trafficking and antigen presentation in the human immune response to Mycobacterium tuberculosis. J Immunol 2004;173:494-506.
111. Martinez FO, Gordon S. TheM1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014;6:13.
112. Mattila JT, Ojo OO, Kepka-Lenhart D et al. Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms. J Immunol 2013;191:773-84.
113. Matty MA, Roca FJ, Cronan MR et al. Adventures within the speckled band: heterogeneity, angiogenesis, and balanced inflammation in the tuberculous granuloma. Immunol Rev 2015;264:276-87.
114. Mayer-Barber KD, Andrade BB, Oland SD et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature 2014;511:99-103.
115. Mayer-Barber KD, Sher A. Cytokine and lipid mediator networks in tuberculosis. Immunol Rev 2015;264:264-75.
116. Mayer-Barber KD, Yan B. Clash of the cytokine titans: counterregulation of interleukin-1 and type I interferon-mediated inflammatory responses. Cell Mol Immunol 2016, DOI: 10.1038/cmi.2016.25.
117. McInnes A, Rennick DM. Interleukin 4 induces cultured monocytes/ macrophages to form giant multinucleated cells. J Exp Med 1988;167:598-611.
118. McNally AK, Anderson JM. Interleukin-4 induces foreign body giant cells from human monocytes/macrophages. Differential lymphokine regulation of macrophage fusion leads to morphological variants of multinucleated giant cells. Am J Pathol 1995;147:1487-99.
119. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010;140:771-6.
120. Meylan PR, Richman DD, Kornbluth RS. Reduced intracellular growth of mycobacteria in human macrophages cultivated at physiologic oxygen pressure. Am Rev Respir Dis 1992;145: 947-53.
121. Milde R, Ritter J, Tennent GA et al. Multinucleated giant cells are specialized for complement-mediated phagocytosis and large target destruction. Cell Rep 2015;13:1937-48.
122. Miller YI, Choi SH, Wiesner P et al. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res 2011;108:235-48.
123. Mishra BB, Moura-Alves P, Sonawane A et al. Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol 2010;12: 1046-63.
124. Mishra BB, Rathinam VA, Martens GW et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1beta. Nat Immunol 2013;14:52-60.
125. Mogilenko DA, Orlov SV, Trulioff AS et al. Endogenous apolipoprotein A-I stabilizes ATP-binding cassette transporter A1 and modulates Toll-like receptor 4 signaling in human macrophages. FASEB J 2012;26:2019-30.
126. Monin L, Khader SA. Chemokines in tuberculosis: the good, the bad and the ugly. Semin Immunol 2014;26:552-8.
127. Moore KJ, Freeman MW. Scavenger receptors in atherosclerosis: beyond lipid uptake. Arterioscl Throm Vas Biol 2006;26: 1702-11.
128. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 2013;13:709-21. Mosser DM. The many faces of macrophage activation. J Leukocyte Biol 2003;73:209-12.
129. Mosser DM. The many faces of macrophage activation. J Leukocyte Biol 2003;73:209-12
130. Movahedi K, Laoui D, Gysemans C et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived fromLy6C(high) monocytes. Cancer Res 2010;70:5728-39.
131. Murray PJ, Allen JE, Biswas SK et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41:14-20.
132. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011;11: 723-37.
133. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity 2014;41:49-61.
134. Oehlers SH, Cronan MR, Scott NR et al. Interception of host angiogenic signalling limits mycobacterial growth. Nature 2015;517:612-5.
135. Ohno H, Zhu G, Mohan VP et al. The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis. Cell Microbiol 2003;5:637-48.
136. Okamoto M, Takeda K, Joetham A et al. Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation. J Exp Med 2008;205:1087-97.
137. O'Leary S, O'Sullivan MP, Keane J. IL-10 blocks phagosome maturation in mycobacterium tuberculosis-infected human macrophages. Am J Resp Cell Mol 2011;45:172-80.
138. Ostrand-Rosenberg S, Sinha P, Beury DW et al. Crosstalk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 2012;22:275-81.
139. Pandey AK, Sassetti CM. Mycobacterial persistence requires the utilization of host cholesterol. P Natl Acad Sci USA 2008;105:4376-80.
140. Peyron P, Vaubourgeix J, Poquet Y et al. Foamy macrophages from tuberculous patients' granulomas constitute a nutrientrich reservoir for M. tuberculosis persistence. PLoS Pathog 2008;4:e1000204.
141. Philips JA, Ernst JD. Tuberculosis pathogenesis and immunity. Annu Rev Pathol 2012;7:353-84.
142. Porcheray F, Viaud S, Rimaniol AC et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 2005;142:481-9.
143. Porta C, Rimoldi M, Raes G et al. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. P Natl Acad Sci USA 2009;106:14978-83.
144. Portugal LR, Fernandes LR, Pietra Pedroso VS et al. Influence of low-density lipoprotein (LDL) receptor on lipid composition, inflammation and parasitism during Toxoplasma gondii infection. Microbes Infect 2008;10:276-84.
145. Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol 2012;12:352-66.
146. Reece ST, Loddenkemper C, Askew DJ et al. Serine protease activity contributes to control of Mycobacterium tuberculosis in hypoxic lung granulomas in mice. J Clin Invest 2010;120: 3365-76.
147. Repasy T, Lee J, Marino S et al. Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo. PLoS Pathog 2013;9:e1003190.
148. Riol-Blanco L, Lazarevic V, Awasthi A et al. IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. J Immunol 2010;184:1710-20.
149. Roach DR, Bean AG, Demangel C et al. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol 2002;168:4620-7.
150. Rubins JB. Alveolar macrophages: wielding the double-edged sword of inflammation. Am J Resp Crit Care 2003;167: 103-4.
151. Russell DG. Who puts the tubercle in tuberculosis?. Nat Rev Microbiol 2007;5:39-47.
152. Russell DG, Cardona PJ, Kim MJ et al. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 2009;10:943-8.
153. Saiga H, Kitada S, Shimada Y et al. Critical role of AIM2 in Mycobacterium tuberculosis infection. Int Immunol 2012;24: 637-44.
154. Saita N, Fujiwara N, Yano I et al. Trehalose 6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis induces corneal angiogenesis in rats. Infect Immun 2000;68:5991-7.
155. Schneider C, Nobs SP, Kurrer M et al. Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat Immunol 2014;15:1026-37.
156. Schreiber HA, Harding JS, Hunt O et al. Inflammatory dendritic cells migrate in and out of transplanted chronic mycobacterial granulomas in mice. J Clin Invest 2011;121:3902-13. Schulz C, Gomez Perdiguero E, Chorro L et al. A lineage ofmyeloid cells independent of Myb and hematopoietic stem cells. Science 2012;336:86-90.
157. Schulz C, Gomez Perdiguero E, Chorro L et al. A lineage ofmyeloid cells independent of Myb and hematopoietic stem cells. Science 2012;336:86-90.
158. Segura E, Amigorena S. Inflammatory dendritic cells in mice and humans. Trends Immunol 2013;34:440-5.
159. Shah S, Bohsali A, Ahlbrand SE et al. Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-beta and AIM2 inflammasome-dependent IL- 1beta production via its ESX-1 secretion system. J Immunol 2013;191:3514-8.
160. Sheedy FJ, Grebe A, Rayner KJ et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat Immunol 2013;14:812-20.
161. Shiloh MU, Manzanillo P, Cox JS. Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection. Cell Host Microbe 2008;3:323-30.
162. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012;122:787-95.
163. Silva AR, Pacheco P, Vieira-de-Abreu A et al. Lipid bodies in oxidized LDL-induced foam cells are leukotriene-synthesizing organelles: a MCP-1/CCL2 regulated phenomenon. Biochim Biophys Acta 2009;1791:1066-75.
164. Silver RF, Walrath J, Lee H et al. Human alveolar macrophage gene responses to Mycobacterium tuberculosis strains H37Ra and H37Rv. Am J Resp Cell Mol 2009;40:491-504.
165. Singh V, Jamwal S, Jain R et al. Mycobacterium tuberculosisdriven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype. Cell Host Microbe 2012;12: 669-81.
166. Skold M, Behar SM. Tuberculosis triggers a tissue-dependent program of differentiation and acquisition of effector functions by circulating monocytes. J Immunol 2008;181:6349-60.
167. Soucie EL,Weng Z, Geirsdottir L et al. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Science 2016;351:aad5510.
168. Srivastava S, Ernst JD, Desvignes L. Beyond macrophages: the diversity of mononuclear cells in tuberculosis. Immunol Rev 2014;262:179-92.
169. Stein M, Keshav S, Harris N et al. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 1992;176:287-92.
170. Stout RD, Suttles J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J Leukocyte Biol 2004;76:509-13.
171. Swirski FK, Libby P, Aikawa E et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 2007;117:195-205.
172. Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscl Throm Vas Biol 2005;25:2255-64.
173. Tacke F, Alvarez D, Kaplan TJ et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 2007;117:185-94.
174. Tanaka A, Emori K, Nagao S et al. Epithelioid granuloma formation requiring no T-cell function. Am J Pathol 1982;106:165-70.
175. Tauber AI. Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Bio 2003;4:897-901.
176. Thurnher M, Ramoner R, Gastl G et al. Bacillus Calmette-Guerin mycobacteria stimulate human blood dendritic cells. Int J Cancer 1997;70:128-34.
177. Tobin DM, Roca FJ, Oh SF et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell 2012;148:434-46.
178. Tobin DM, Vary JC, Jr, Ray JP et al. The lta4h locus modulates susceptibility tomycobacterial infection in zebrafish and humans. Cell 2010;140:717-30.
179. Tripathi C, Tewari BN, Kanchan RK et al. Macrophages are recruited to hypoxic tumor areas and acquire a pro-angiogenic M2-polarized phenotype via hypoxic cancer cell derived cytokines Oncostatin M and Eotaxin. Oncotarget 2014;5: 5350-68.
180. Tsiganov EN, Verbina EM, Radaeva TV et al. Gr-1dimCD11b+ immaturemyeloid- derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice. J Immunol 2014;192:4718-27.
181. Tsuda T, Dannenberg AM, Ando M et al. Mononuclear cell turnover in chronic inflammation: studies on tritiated thymidine-labeled cells in blood, tuberculin traps, and dermal BCG lesions of rabbits. Am J Pathol 1976;83: 255-68.
182. Tung YC, Ou TT, Tsai WC. Defective Mycobacterium tuberculosis antigen presentation by monocytes from tuberculosis patients. Int J Tuberc Lung D 2013;17: 1229-34.
183. Turner J, Gonzalez-Juarrero M, Ellis DL et al. In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J Immunol 2002;169:6343-51.
184. Umemura M, Yahagi A, Hamada S et al. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol 2007;178:3786-96.
185. van Furth R, Cohn ZA, Hirsch JG et al. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. B World Health Organ 1972;46:845-52.
186. Varol C, Mildner A, Jung S.Macrophages: development and tissue specialization. Annu Rev Immunol 2015;33:643-75.
187. Verreck FA, de Boer T, Langenberg DM et al. Human IL-23- producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. P Natl Acad Sci USA 2004;101:4560-5.
188. Via LE, Lin PL, Ray SM et al. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun 2008;76:2333-40.
189. Walther TC, Farese RV, Jr. Lipid droplets and cellular lipid metabolism. Annu Rev Biochem 2012;81:687-714.
190. Wassermann R, Gulen MF, Sala C et al. Mycobacterium tuberculosis differentially activates cgas- and inflammasomedependent intracellular immune responses through ESX-1. Cell Host Microbe 2015;17:799-810.
191. Welsh KJ, Risin SA, Actor JK et al. Immunopathology of postprimary tuberculosis: increased T-regulatory cells and DEC-205- positive foamy macrophages in cavitary lesions. Clin Dev Immunol 2011;2011:307631.
192. WHO.World Health Organization. Global Tuberculosis Report 2015. Geneva, Switzerland: WHO Press.
193. Williams GT, Williams WJ. Granulomatous inflammation-a review. J Clin Pathol 1983;36:723-33.
194. Wolf AJ, Linas B, Trevejo-Nunez GJ et al. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J Immunol 2007;179:2509-19.
195. Wong KL, Yeap WH, Tai JJ et al. The three human monocyte subsets: implications for health and disease. Immunol Res 2012;53:41-57.
196. Xue J, Schmidt SV, Sander J et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 2014;40:274-88.
197. Xue Q, Lu Y, Eisele MR et al. Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation. Sci Signal 2015;8:ra59.
198. Yamada M, Naito M, Takahashi K. Kupffer cell proliferation and glucan-induced granuloma formation in mice depleted of blood monocytes by strontium-89. J Leukocyte Biol 1990;47:195-205.
199. Yang CT, Cambier CJ, Davis JM et al. Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages. Cell Host Microbe 2012;12:301-12.
200. Yona S, Kim KW, Wolf Y et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 2013;38:79-91.
201. Yvan-Charvet L, Pagler T, Gautier EL et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 2010;328:1689-93.
202. Yvan-Charvet L,Welch C, Pagler TA et al. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via tolllike receptors, and neutrophil infiltration of atherosclerotic lesions. Circulation 2008;118:1837-47.
203. Zhu X, Owen JS, Wilson MD et al. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. J Lipid Res 2010;51: 3196-206.