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The multiple roles of monocyte subsets in steady state and inflammation

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Abstract

Monocytes participate importantly in immunity. Produced in the bone marrow and released into the blood, they circulate in blood or reside in a spleen reservoir before entering tissue and giving rise to macrophages or dendritic cells. Monocytes are more than transitional cells that adapt to a particular tissue environment indiscriminately. Accumulating evidence now indicates that monocytes are heterogeneous in several species and are themselves predetermined for particular function in the steady state and inflammation. Future therapeutics may harness this heterogeneity to target harmful functions while sparing those that are beneficial. Here, we review recent advances on the ontogeny and function of monocytes and their subsets in humans and mice.

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References

  1. Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692

    Article  PubMed  CAS  Google Scholar 

  2. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964

    Article  PubMed  CAS  Google Scholar 

  3. Sabin FR, Doan CA (1927) The relation of monocytes and clasmatocytes to early infection in rabbits with bovine Tubercle Bacilli. J Exp Med 46:627–644

    Article  PubMed  CAS  Google Scholar 

  4. van Furth R, Cohn ZA (1968) The origin and kinetics of mononuclear phagocytes. J Exp Med 128:415–435

    Article  PubMed  Google Scholar 

  5. Yasaka T, Mantich NM, Boxer LA, Baehner RL (1981) Functions of human monocyte and lymphocyte subsets obtained by countercurrent centrifugal elutriation: differing functional capacities of human monocyte subsets. J Immunol 127:1515–1518

    PubMed  CAS  Google Scholar 

  6. Figdor CG, Bont WS, Touw I, de Roos J, Roosnek EE, de Vries JE (1982) Isolation of functionally different human monocytes by counterflow centrifugation elutriation. Blood 60:46–53

    PubMed  CAS  Google Scholar 

  7. Akiyama Y, Miller PJ, Thurman GB, Neubauer RH, Oliver C, Favilla T, Beman JA, Oldham RK, Stevenson HC (1983) Characterization of a human blood monocyte subset with low peroxidase activity. J Clin Invest 72:1093–1105

    Article  PubMed  CAS  Google Scholar 

  8. Schreiber AD, Kelley M, Dziarski A, Levinson AI (1983) Human monocyte functional heterogeneity: monocyte fractionation by discontinuous albumin gradient centrifugation. Immunology 49:231–238

    PubMed  CAS  Google Scholar 

  9. Weiner RS, Mason RR (1984) Subfractionation of human blood monocyte subsets with Percoll. Exp Hematol 12:800–804

    PubMed  CAS  Google Scholar 

  10. Akiyama Y, Stevenson GW, Schlick E, Matsushima K, Miller PJ, Stevenson HC (1985) Differential ability of human blood monocyte subsets to release various cytokines. J Leukoc Biol 37:519–530

    PubMed  CAS  Google Scholar 

  11. Elias JA, Chien P, Gustilo KM, Schreiber AD (1985) Differential interleukin-1 elaboration by density-defined human monocyte subpopulations. Blood 66:298–301

    PubMed  CAS  Google Scholar 

  12. Esa AH, Noga SJ, Donnenberg AD, Hess AD (1986) Immunological heterogeneity of human monocyte subsets prepared by counterflow centrifugation elutriation. Immunology 59:95–99

    PubMed  CAS  Google Scholar 

  13. Grage-Griebenow E, Flad HD, Ernst M (2001) Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol 69:11–20

    PubMed  CAS  Google Scholar 

  14. Zembala M, Uracz W, Ruggiero I, Mytar B, Pryjma J (1984) Isolation and functional characteristics of FcR+ and FcR- human monocyte subsets. J Immunol 133:1293–1299

    PubMed  CAS  Google Scholar 

  15. Pryjma J, Pituch-Noworolska A, Ruggiero I, Zembala M (1985) The regulation of polyclonal immunoglobulin synthesis by FcR+ and FcR− monocyte subsets. Clin Immunol Immunopathol 37:245–252

    Article  PubMed  CAS  Google Scholar 

  16. Grage-Griebenow E, Lorenzen D, Fetting R, Flad HD, Ernst M (1993) Phenotypical and functional characterization of Fc gamma receptor I (CD64)-negative monocytes, a minor human monocyte subpopulation with high accessory and antiviral activity. Eur J Immunol 23:3126–3135

    Article  PubMed  CAS  Google Scholar 

  17. Grage-Griebenow E, Flad HD, Ernst M (1996) Fc gamma receptor I (CD64)-negative human monocytes are potent accessory cells in viral antigen-induced T cell activation and exhibit high IFN-alpha-producing capacity. J Leukoc Biol 60:389–396

    PubMed  CAS  Google Scholar 

  18. Grage-Griebenow E, Baran J, Loppnow H, Los M, Ernst M, Flad HD, Pryjma J (1997) An Fc gamma receptor I (CD64)-negative subpopulation of human peripheral blood monocytes is resistant to killing by antigen-activated CD4-positive cytotoxic T cells. Eur J Immunol 27:2358–2365

    Article  PubMed  CAS  Google Scholar 

  19. Grage-Griebenow E, Flad HD, Ernst M, Bzowska M, Skrzeczynska J, Pryjma J (2000) Human MO subsets as defined by expression of CD64 and CD16 differ in phagocytic activity and generation of oxygen intermediates. Immunobiology 202:42–50

    PubMed  CAS  Google Scholar 

  20. Grage-Griebenow E, Zawatzky R, Kahlert H, Brade L, Flad H, Ernst M (2001) Identification of a novel dendritic cell-like subset of CD64(+)/CD16(+) blood monocytes. Eur J Immunol 31:48–56

    Article  PubMed  CAS  Google Scholar 

  21. Passlick B, Flieger D, Ziegler-Heitbrock HW (1989) Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74:2527–2534

    PubMed  CAS  Google Scholar 

  22. Ziegler-Heitbrock HW, Passlick B, Flieger D (1988) The monoclonal antimonocyte antibody My4 stains B lymphocytes and two distinct monocyte subsets in human peripheral blood. Hybridoma 7:521–527

    Article  PubMed  CAS  Google Scholar 

  23. Ziegler-Heitbrock HW, Fingerle G, Strobel M, Schraut W, Stelter F, Schutt C, Passlick B, Pforte A (1993) The novel subset of CD14+/CD16+ blood monocytes exhibits features of tissue macrophages. Eur J Immunol 23:2053–2058

    Article  PubMed  CAS  Google Scholar 

  24. Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, Espevik T, Ziegler-Heitbrock L (2002) The proinflammatory CD14 + CD16 + DR++ monocytes are a major source of TNF. J Immunol 168:3536–3542

    PubMed  CAS  Google Scholar 

  25. Frankenberger M, Sternsdorf T, Pechumer H, Pforte A, Ziegler-Heitbrock HW (1996) Differential cytokine expression in human blood monocyte subpopulations: a polymerase chain reaction analysis. Blood 87:373–377

    PubMed  CAS  Google Scholar 

  26. Sanchez-Torres C, Garcia-Romo GS, Cornejo-Cortes MA, Rivas-Carvalho A, Sanchez-Schmitz G (2001) CD16+ and CD16− human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells. Int Immunol 13:1571–1581

    Article  PubMed  CAS  Google Scholar 

  27. Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schakel K (2002) The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting. J Exp Med 196:517–527

    Article  PubMed  CAS  Google Scholar 

  28. Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW, Gabuzda D (2003) Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med 197:1701–1707

    Article  PubMed  CAS  Google Scholar 

  29. Ziegler-Heitbrock L (2007) The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 81:584–592

    Article  PubMed  CAS  Google Scholar 

  30. Horelt A, Belge KU, Steppich B, Prinz J, Ziegler-Heitbrock L (2002) The CD14+ CD16+ monocytes in erysipelas are expanded and show reduced cytokine production. Eur J Immunol 32:1319–1327

    Article  PubMed  CAS  Google Scholar 

  31. Fingerle-Rowson G, Auers J, Kreuzer E, Fraunberger P, Blumenstein M, Ziegler-Heitbrock LH (1998) Expansion of CD14+ CD16+ monocytes in critically ill cardiac surgery patients. Inflammation 22:367–379

    Article  PubMed  CAS  Google Scholar 

  32. Mizuno K, Toma T, Tsukiji H, Okamoto H, Yamazaki H, Ohta K, Ohta K, Kasahara Y, Koizumi S, Yachie A (2005) Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation. Clin Exp Immunol 142:461–470

    PubMed  CAS  Google Scholar 

  33. Noel JG, Osterburg A, Wang Q, Guo X, Byrum D, Schwemberger S, Goetzman H, Caldwell CC, Ogle CK (2007) Thermal injury elevates the inflammatory monocyte subpopulation in multiple compartments. Shock 28:684–693

    PubMed  CAS  Google Scholar 

  34. Skrzeczynska-Moncznik J, Bzowska M, Loseke S, Grage-Griebenow E, Zembala M, Pryjma J (2008) Peripheral blood CD14 high CD16+ monocytes are main producers of IL-10. Scand J Immunol 67:152–159

    Article  PubMed  CAS  Google Scholar 

  35. Wildgruber M, Lee H, Chudnovskiy A, Yoon TJ, Etzrodt M, Pittet MJ, Nahrendorf M, Croce K, Libby P, Weissleder R, Swirski FK (2009) Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors. PLoS One 4:e5663

    Article  PubMed  CAS  Google Scholar 

  36. Tsujioka H, Imanishi T, Ikejima H, Kuroi A, Takarada S, Tanimoto T, Kitabata H, Okochi K, Arita Y, Ishibashi K, Komukai K, Kataiwa H, Nakamura N, Hirata K, Tanaka A, Akasaka T (2009) Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J Am Coll Cardiol 54:130–138

    Article  PubMed  Google Scholar 

  37. Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, Hill BJ, Noto A, Ancuta P, Peretz Y, Fonseca SG, Van Grevenynghe J, Boulassel MR, Bruneau J, Shoukry NH, Routy JP, Douek DC, Haddad EK, Sekaly RP (2010) Programmed death-1-induced interleukin-10 production by monocytes impairs CD4(+) T cell activation during HIV infection. Nat Med 16:452–459

    Article  PubMed  CAS  Google Scholar 

  38. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, Littman DR (2000) Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20:4106–4114

    Article  PubMed  CAS  Google Scholar 

  39. Palframan RT, Jung S, Cheng G, Weninger W, Luo Y, Dorf M, Littman DR, Rollins BJ, Zweerink H, Rot A, von Andrian UH (2001) Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med 194:1361–1373

    Article  PubMed  CAS  Google Scholar 

  40. Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82

    Article  PubMed  CAS  Google Scholar 

  41. Akashi K, Traver D, Miyamoto T, Weissman IL (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404:193–197

    Article  PubMed  CAS  Google Scholar 

  42. Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, Shizuru JA, Weissman IL (2003) Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 21:759–806

    Article  PubMed  CAS  Google Scholar 

  43. Fogg DK, Sibon C, Miled C, Jung S, Aucouturier P, Littman DR, Cumano A, Geissmann F (2006) A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311:83–87

    Article  PubMed  CAS  Google Scholar 

  44. Auffray C, Fogg DK, Narni-Mancinelli E, Senechal B, Trouillet C, Saederup N, Leemput J, Bigot K, Campisi L, Abitbol M, Molina T, Charo I, Hume DA, Cumano A, Lauvau G, Geissmann F (2009) CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation. J Exp Med 206:595–606

    Article  PubMed  CAS  Google Scholar 

  45. Onai N, Obata-Onai A, Schmid MA, Ohteki T, Jarrossay D, Manz MG (2007) Identification of clonogenic common Flt3+ M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol 8:1207–1216

    Article  PubMed  CAS  Google Scholar 

  46. Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, Dakic A, Carotta S, O’Keeffe M, Bahlo M, Papenfuss A, Kwak JY, Wu L, Shortman K (2007) Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 8:1217–1226

    Article  PubMed  CAS  Google Scholar 

  47. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM, Yao K, Chu FF, Randolph GJ, Rudensky AY, Nussenzweig M (2009) In vivo analysis of dendritic cell development and homeostasis. Science 324:392–397

    Article  PubMed  CAS  Google Scholar 

  48. Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137:1142–1162

    Article  PubMed  CAS  Google Scholar 

  49. Steinman RM, Cohn ZA (1974) Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med 139:380–397

    Article  PubMed  CAS  Google Scholar 

  50. Steinman RM, Lustig DS, Cohn ZA (1974) Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo. J Exp Med 139:1431–1445

    Article  PubMed  CAS  Google Scholar 

  51. Alvarez D, Vollmann EH, von Andrian UH (2008) Mechanisms and consequences of dendritic cell migration. Immunity 29:325–342

    Article  PubMed  CAS  Google Scholar 

  52. Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ (2004) Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 172:4410–4417

    PubMed  Google Scholar 

  53. Varol C, Landsman L, Fogg DK, Greenshtein L, Gildor B, Margalit R, Kalchenko V, Geissmann F, Jung S (2007) Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204:171–180

    Article  PubMed  CAS  Google Scholar 

  54. Liu K, Waskow C, Liu X, Yao K, Hoh J, Nussenzweig M (2007) Origin of dendritic cells in peripheral lymphoid organs of mice. Nat Immunol 8:578–583

    Article  PubMed  CAS  Google Scholar 

  55. Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ (2009) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325:612–616

    Article  PubMed  CAS  Google Scholar 

  56. Serbina NV, Pamer EG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7:311–317

    Article  PubMed  CAS  Google Scholar 

  57. Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, Weisberg SP, Mack M, Charo IF (2007) Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 117:902–909

    Article  PubMed  CAS  Google Scholar 

  58. Ishibashi M, Hiasa K, Zhao Q, Inoue S, Ohtani K, Kitamoto S, Tsuchihashi M, Sugaya T, Charo IF, Kura S, Tsuzuki T, Ishibashi T, Takeshita A, Egashira K (2004) Critical role of monocyte chemoattractant protein-1 receptor CCR2 on monocytes in hypertension-induced vascular inflammation and remodeling. Circ Res 94:1203–1210

    Article  PubMed  CAS  Google Scholar 

  59. Drevets DA, Dillon MJ, Schawang JS, Van Rooijen N, Ehrchen J, Sunderkotter C, Leenen PJ (2004) The Ly-6Chigh monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice. J Immunol 172:4418–4424

    PubMed  CAS  Google Scholar 

  60. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047

    Article  PubMed  CAS  Google Scholar 

  61. Swirski FK, Pittet MJ, Kircher MF, Aikawa E, Jaffer FA, Libby P, Weissleder R (2006) Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease. Proc Natl Acad Sci USA 103:10340–10345

    Article  PubMed  CAS  Google Scholar 

  62. Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ (2007) Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 117:195–205

    Article  PubMed  CAS  Google Scholar 

  63. Combadiere C, Potteaux S, Rodero M, Simon T, Pezard A, Esposito B, Merval R, Proudfoot A, Tedgui A, Mallat Z (2008) Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 117:1649–1657

    Article  PubMed  CAS  Google Scholar 

  64. Wu H, Gower RM, Wang H, Perrard XY, Ma R, Bullard DC, Burns AR, Paul A, Smith CW, Simon SI, Ballantyne CM (2009) Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 119:2708–2717

    Article  PubMed  CAS  Google Scholar 

  65. Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, Garin A, Liu J, Mack M, van Rooijen N, Lira SA, Habenicht AJ, Randolph GJ (2007) Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117:185–194

    Article  PubMed  CAS  Google Scholar 

  66. Galkina E, Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol 27:165–197

    Article  PubMed  CAS  Google Scholar 

  67. Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M, Frankenberger M, Weber KS, Ziegler-Heitbrock HW (2000) Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 67:699–704

    PubMed  CAS  Google Scholar 

  68. Weber C, Zernecke A, Libby P (2008) The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat Rev Immunol 8:802–815

    Article  PubMed  CAS  Google Scholar 

  69. Jia T, Serbina NV, Brandl K, Zhong MX, Leiner IM, Charo IF, Pamer EG (2008) Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. J Immunol 180:6846–6853

    PubMed  CAS  Google Scholar 

  70. Le Borgne M, Etcharts N, Goubier A, Lira SA, Sirard JC, van Rooijen N, Caux C, Ait-Yahia S, Vicari A, Kaiserlian D, Dubois B (2006) Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo. Immunity 24:191–201

    Article  PubMed  CAS  Google Scholar 

  71. Gautier EL, Jakubzick C, Randolph GJ (2009) Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis. Arterioscler Thromb Vasc Biol 29:1412–1418

    Article  PubMed  CAS  Google Scholar 

  72. Saederup N, Chan L, Lira SA, Charo IF (2008) Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2−/− mice: evidence for independent chemokine functions in atherogenesis. Circulation 117:1642–1648

    Article  PubMed  CAS  Google Scholar 

  73. Combadiere C, Potteaux S, Gao JL, Esposito B, Casanova S, Lee EJ, Debre P, Tedgui A, Murphy PM, Mallat Z (2003) Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice. Circulation 107:1009–1016

    Article  PubMed  CAS  Google Scholar 

  74. Lesnik P, Haskell CA, Charo IF (2003) Decreased atherosclerosis in CX3CR1−/− mice reveals a role for fractalkine in atherogenesis. J Clin Invest 111:333–340

    PubMed  CAS  Google Scholar 

  75. An G, Wang H, Tang R, Yago T, McDaniel JM, McGee S, Huo Y, Xia L (2008) P-selectin glycoprotein ligand-1 is highly expressed on Ly-6Chi monocytes and a major determinant for Ly-6Chi monocyte recruitment to sites of atherosclerosis in mice. Circulation 117:3227–3237

    Article  PubMed  CAS  Google Scholar 

  76. Libby P, Nahrendorf M, Pittet MJ, Swirski FK (2008) Diversity of denizens of the atherosclerotic plaque: not all monocytes are created equal. Circulation 117:3168–3170

    Article  PubMed  Google Scholar 

  77. Swirski FK, Weissleder R, Pittet MJ (2009) Heterogeneous in vivo behavior of monocyte subsets in atherosclerosis. Arterioscler Thromb Vasc Biol 29:1424–1432

    Article  PubMed  CAS  Google Scholar 

  78. Woollard KJ, Geissmann F (2010) Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7:77–86

    Article  PubMed  Google Scholar 

  79. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S (2009) CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 113:963–972

    Article  PubMed  CAS  Google Scholar 

  80. Serbina NV, Jia T, Hohl TM, Pamer EG (2008) Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 26:421–452

    Article  PubMed  CAS  Google Scholar 

  81. Strauss-Ayali D, Conrad SM, Mosser DM (2007) Monocyte subpopulations and their differentiation patterns during infection. J Leukoc Biol 82:244–252

    Article  PubMed  CAS  Google Scholar 

  82. Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG (2003) TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19:59–70

    Article  PubMed  CAS  Google Scholar 

  83. Dunay IR, Damatta RA, Fux B, Presti R, Greco S, Colonna M, Sibley LD (2008) Gr1(+) inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity 29:306–317

    Article  PubMed  CAS  Google Scholar 

  84. Barbalat R, Lau L, Locksley RM, Barton GM (2009) Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat Immunol 10:1200–1207

    Article  PubMed  CAS  Google Scholar 

  85. Serbina NV, Kuziel W, Flavell R, Akira S, Rollins B, Pamer EG (2003) Sequential MyD88-independent and -dependent activation of innate immune responses to intracellular bacterial infection. Immunity 19:891–901

    Article  PubMed  CAS  Google Scholar 

  86. Robben PM, LaRegina M, Kuziel WA, Sibley LD (2005) Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis. J Exp Med 201:1761–1769

    Article  PubMed  CAS  Google Scholar 

  87. Arnold L, Henry A, Poron F, Baba-Amer Y, van Rooijen N, Plonquet A, Gherardi RK, Chazaud B (2007) Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204:1057–1069

    Article  PubMed  CAS  Google Scholar 

  88. Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, Sarnacki S, Cumano A, Lauvau G, Geissmann F (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:666–670

    Article  PubMed  CAS  Google Scholar 

  89. Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne CM, Kubes P (2006) Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 203:2569–2575

    Article  PubMed  CAS  Google Scholar 

  90. Ryschich E, Kerkadze V, Lizdenis P, Paskauskas S, Knaebel HP, Gross W, Gebhard MM, Buchler MW, Schmidt J (2006) Active leukocyte crawling in microvessels assessed by digital time-lapse intravital microscopy. J Surg Res 135:291–296

    Article  PubMed  CAS  Google Scholar 

  91. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K (2010) Development of monocytes, macrophages, and dendritic cells. Science 327:656–661

    Article  PubMed  CAS  Google Scholar 

  92. Copin R, De Baetselier P, Carlier Y, Letesson JJ, Muraille E (2007) MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection. J Immunol 178:5182–5191

    PubMed  CAS  Google Scholar 

  93. Narni-Mancinelli E, Campisi L, Bassand D, Cazareth J, Gounon P, Glaichenhaus N, Lauvau G (2007) Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. J Exp Med 204:2075–2087

    Article  PubMed  CAS  Google Scholar 

  94. Aldridge JRJ, Moseley CE, Boltz DA, Negovetich NJ, Reynolds C, Franks J, Brown SA, Doherty PC, Webster RG, Thomas PG (2009) TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci USA 106:5306–5311

    Article  PubMed  Google Scholar 

  95. Landsman L, Varol C, Jung S (2007) Distinct differentiation potential of blood monocyte subsets in the lung. J Immunol 178:2000–2007

    PubMed  CAS  Google Scholar 

  96. Mantovani A, Garlanda C, Locati M (2009) Macrophage diversity and polarization in atherosclerosis: a question of balance. Arterioscler Thromb Vasc Biol 29:1419–1423

    Article  PubMed  CAS  Google Scholar 

  97. Martinez FO, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177:7303–7311

    PubMed  CAS  Google Scholar 

  98. Lin SL, Castano AP, Nowlin BT, Lupher MLJ, Duffield JS (2009) Bone marrow Ly6Chigh monocytes are selectively recruited to injured kidney and differentiate into functionally distinct populations. J Immunol 183:6733–6743

    Article  PubMed  CAS  Google Scholar 

  99. Dominguez PM, Ardavin C (2010) Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation. Immunol Rev 234:90–104

    Article  PubMed  CAS  Google Scholar 

  100. Jakubzick C, Tacke F, Ginhoux F, Wagers AJ, van Rooijen N, Mack M, Merad M, Randolph GJ (2008) Blood monocyte subsets differentially give rise to CD103+ and CD103− pulmonary dendritic cell populations. J Immunol 180:3019–3027

    PubMed  CAS  Google Scholar 

  101. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y, Luche H, Fehling HJ, Hardt WD, Shakhar G, Jung S (2009) Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31:502–512

    Article  PubMed  CAS  Google Scholar 

  102. Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M, Dai XM, Stanley ER, Randolph GJ, Merad M (2006) Langerhans cells arise from monocytes in vivo. Nat Immunol 7:265–273

    Article  PubMed  CAS  Google Scholar 

  103. Chorro L, Sarde A, Li M, Woollard KJ, Chambon P, Malissen B, Kissenpfennig A, Barbaroux JB, Groves R, Geissmann F (2009) Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med 206:3089–3100

    Article  PubMed  CAS  Google Scholar 

  104. Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch UK, Mack M, Heikenwalder M, Bruck W, Priller J, Prinz M (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10:1544–1553

    Article  PubMed  CAS  Google Scholar 

  105. Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P, Restifo NP, Zanovello P (2000) Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96:3838–3846

    PubMed  CAS  Google Scholar 

  106. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, Basso G, Brombacher F, Borrello I, Zanovello P, Bicciato S, Bronte V (2006) Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 116:2777–2790

    Article  PubMed  CAS  Google Scholar 

  107. Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, De Baetselier P, Van Ginderachter JA (2008) Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111:4233–4244

    Article  PubMed  CAS  Google Scholar 

  108. Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM, Chen SH (2006) Gr-1 + CD115 + immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66:1123–1131

    Article  PubMed  CAS  Google Scholar 

  109. Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, Hoffmann R, Lang R, Haniffa M, Collin M, Tacke F, Habenicht AJ, Ziegler-Heitbrock L, Randolph GJ (2010) Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115:e10–e19

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was funded by NIH grant 1R01HL095612 (to FKS) and an AHA postdoctoral fellowship (to CSR).

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  1. Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge St., Boston, MA, 02114, USA

    Clinton S. Robbins & Filip K. Swirski

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  1. Clinton S. Robbins
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  2. Filip K. Swirski
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Correspondence to Filip K. Swirski.

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Robbins, C.S., Swirski, F.K. The multiple roles of monocyte subsets in steady state and inflammation. Cell. Mol. Life Sci. 67, 2685–2693 (2010). https://doi.org/10.1007/s00018-010-0375-x

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  • DOI: https://doi.org/10.1007/s00018-010-0375-x

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