Polarization and Functional Plasticity of Macrophages in Regulating Innate Immune Response

doi:10.1007/s12204-014-1561-z

摘要/Abstract

摘要： Innate immune system is the first line of resistance that protects the host body from invasion of pathogens. During this innate immune response process, macrophages are well known to be the powerful leading players located throughout the body in defecting attacks. Originated from bone marrow, monocyte-macrophage lineage still manifests hallmarks of plasticity and diversity. Toll-like receptor (TLR) or interferon gamma (IFNγ) drives macrophages into M1 (classical) activation while IL-4/IL-13 or IL-10 induces M2 (alternative) activation. Different phenotypes of macrophages have distinct biological functions, transcriptional profiles, signaling pathways and cytokines along with chemokine framework. Classical M1 macrophages show strong pro-inflammatory and antimicrobial abilities while M2 macrophages are skilled at anti-inflammation, wound healing and fibrosis. Researches have shown that under different pathological conditions, macrophages are programmed to be different phenotypic subsets and play disparate immunomodulation. However, under the intricate microenvironment, there might be mixed populations instead of a kind of unique phenotypic macrophages. Evidences also show that macrophages can be converted from one phenotype to another according to microenvironmental signals (cytokines, chemokines, growth factors, and microbial-associated molecule patterns). A better understanding of the mechanisms of plasticity and polarization of macrophages will shine new lights into the mechanisms underlying the innate inflammation diseases and suggest promising therapeutic targets.

关键词: macrophages, plasticity, polarization, innate immunity

Abstract: Innate immune system is the first line of resistance that protects the host body from invasion of pathogens. During this innate immune response process, macrophages are well known to be the powerful leading players located throughout the body in defecting attacks. Originated from bone marrow, monocyte-macrophage lineage still manifests hallmarks of plasticity and diversity. Toll-like receptor (TLR) or interferon gamma (IFNγ) drives macrophages into M1 (classical) activation while IL-4/IL-13 or IL-10 induces M2 (alternative) activation. Different phenotypes of macrophages have distinct biological functions, transcriptional profiles, signaling pathways and cytokines along with chemokine framework. Classical M1 macrophages show strong pro-inflammatory and antimicrobial abilities while M2 macrophages are skilled at anti-inflammation, wound healing and fibrosis. Researches have shown that under different pathological conditions, macrophages are programmed to be different phenotypic subsets and play disparate immunomodulation. However, under the intricate microenvironment, there might be mixed populations instead of a kind of unique phenotypic macrophages. Evidences also show that macrophages can be converted from one phenotype to another according to microenvironmental signals (cytokines, chemokines, growth factors, and microbial-associated molecule patterns). A better understanding of the mechanisms of plasticity and polarization of macrophages will shine new lights into the mechanisms underlying the innate inflammation diseases and suggest promising therapeutic targets.

Key words: macrophages, plasticity, polarization, innate immunity

中图分类号:

Q 291

LIU Wen-jun (刘雯君), GAO Wei-qiang (高维强), KONG Xiao-ni*(孔晓妮). Polarization and Functional Plasticity of Macrophages in Regulating Innate Immune Response[J]. 上海交通大学学报（英文版）, 2014, 19(6): 646-650.

LIU Wen-jun (刘雯君), GAO Wei-qiang (高维强), KONG Xiao-ni*(孔晓妮). Polarization and Functional Plasticity of Macrophages in Regulating Innate Immune Response[J]. Journal of shanghai Jiaotong University (Science), 2014, 19(6): 646-650.

参考文献

[1] Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system [J]. Science,2010, 327(5963): 291-295.
[2] Newton K, Dixit V M. Signaling in innate immunity and inflammation [J]. Cold Spring Harbor Perspectives in Biology, 2012, 4(3): a006049.
[3] Galli S J, Borregaard N, Wynn T A. Phenotypic and functional plasticity of cells of innate immunity:Macrophages, mast cells and neutrophils [J]. Nature Immunology, 2011, 12(11): 1035-1044.
[4] Biswas S K, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm [J]. Nature Immunology, 2010, 11(10): 889-896.
[5] Sica A, Mantovani A.Macrophage plasticity and polarization:In vivo veritas [J]. The Journal of Clinical Investigation, 2012, 122(3): 787-795.
[6] Gabrilovich D I, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system [J].Nature Reviews Immunology, 2009, 9(3): 162-174.
[7] Kusmartsev S, Gabrilovich D I. STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion [J]. The Journal of Immunology, 2005,174(8): 4880-4891.
[8] Biswas S K, Lopez-Collazo E. Endotoxin tolerance:New mechanisms, molecules and clinical significance[J]. Trends in Immunology, 2009, 30(10): 475-487.
[9] Stout R D, Jiang C, Matta B, et al. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences [J].The Journal of Immunology, 2005, 175(1): 342-349.
[10] Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways[J]. Cellular Signalling, 2014, 26(2): 192-197.
[11] Lumeng C N, Bodzin J L, Saltiel A R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization [J]. The Journal of Clinical Investigation, 2007, 117(1): 175-184.
[12] Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization [J]. Trends in Immunology,2004, 25(12): 677-686.
[13] Sierra-Filardi E, Nieto C, Dominguez-Soto A, et al. CCL2 shapes macrophage polarization by GM-CSF and M-CSF: Identification of CCL2/CCR2-dependent gene expression profile [J]. The Journal of Immunology,2014, 192(8): 3858-3867.
[14] Sica A, Invernizzi P, Mantovani A. Macrophage plasticity and polarization in liver homeostasis and pathology [J]. Hepatology, 2014, 59(5): 2034-2042.
[15] Murray P J, Wynn T A. Protective and pathogenic functions of macrophage subsets [J]. Nature Reviews Immunology, 2011, 11(11): 723-737.
[16] Mantovani A, Biswas S, Galdiero M R, et al. Macrophage plasticity and polarization in tissue repair and remodelling [J]. The Journal of Pathology, 2013,229(2): 176-185.
[17] Kawanishi N, Yano H, Yokogawa Y, et al. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice [J].Exercise Immunology Review, 2010, 16: 105-118.
[18] Stout R D, Suttles J. Functional plasticity of macrophages: Reversible adaptation to changing microenvironments[J]. Journal of Leukocyte Biology,2004, 76(3): 509-513.
[19] Jenkins S J, Ruckerl D, Cook P C, et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation [J].Science, 2011, 332(6035): 1284-1288.
[20] Aziz A, Soucie E, Sarrazin S, et al. MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages [J]. Science, 2009, 326(5954): 867-871.