Mantovani, B., Rabinovitch, M. & Nussenzweig, V. Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG). J. Exp. Med.135, 780–792 (1972). CASPubMedPubMed Central Google Scholar
Erwig, L. P. & Henson, P. M. Clearance of apoptotic cells by phagocytes. Cell Death Differ.15, 243–250 (2008). CASPubMed Google Scholar
Hajishengallis, G. & Lambris, J. D. Microbial manipulation of receptor crosstalk in innate immunity. Nature Rev. Immunol.11, 187–200 (2011). CAS Google Scholar
Gordon, S. & Taylor, P. R. Monocyte and macrophage heterogeneity. Nature Rev. Immunol.5, 953–964 (2005). CAS Google Scholar
McGaha, T. L., Chen, Y., Ravishankar, B., van Rooijen, N. & Karlsson, M. C. Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood117, 5403–5412 (2011). CASPubMed Google Scholar
Iannacone, M. et al. Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature465, 1079–1083 (2010). CASPubMedPubMed Central Google Scholar
Junt, T. et al. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature450, 110–114 (2007). CASPubMed Google Scholar
Geissmann, F., Gordon, S., Hume, D. A., Mowat, A. M. & Randolph, G. J. Unravelling mononuclear phagocyte heterogeneity. Nature Rev. Immunol.10, 453–460 (2010). CAS Google Scholar
Cros, J. et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity33, 375–386 (2010). CASPubMedPubMed Central Google Scholar
Sutterwala, F. S., Noel, G. J., Clynes, R. & Mosser, D. M. Selective suppression of interleukin-12 induction after macrophage receptor ligation. J. Exp. Med.185, 1977–1985 (1997). CASPubMedPubMed Central Google Scholar
Sutterwala, F. S., Noel, G. J., Salgame, P. & Mosser, D. M. Reversal of proinflammatory responses by ligating the macrophage Fcγ receptor type I. J. Exp. Med.188, 217–222 (1998). CASPubMedPubMed Central Google Scholar
Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol.8, 958–969 (2008). CAS Google Scholar
Murray, P. J. & Wynn, T. A. Obstacles and opportunities for understanding macrophage polarization. J. Leukoc. Biol.89, 557–563 (2011). CASPubMedPubMed Central Google Scholar
Hagemann, T. et al. “Re-educating” tumor-associated macrophages by targeting NF-κB. J. Exp. Med.205, 1261–1268 (2008). This study shows that activation of NF-κB by IL-1R and MYD88 signalling is required to maintain the immunosuppressive function of TAMs. In the absence of NF-κB signalling, TAMs adopt a 'classically' activated phenotype and kill tumour cells. CASPubMedPubMed Central Google Scholar
Rutschman, R. et al. Cutting edge: Stat6-dependent substrate depletion regulates nitric oxide production. J.Immunol.166, 2173–2177 (2001). CAS Google Scholar
Kawanishi, N., Yano, H., Yokogawa, Y. & Suzuki, K. 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. Exerc. Immunol. Rev.16, 105–118 (2010). PubMed Google Scholar
Mylonas, K. J., Nair, M. G., Prieto-Lafuente, L., Paape, D. & Allen, J. E. Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing. J. Immunol.182, 3084–3094 (2009). CASPubMed Google Scholar
Stout, R. D. et al. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J. Immunol.175, 342–349 (2005). CASPubMed Google Scholar
Stout, R. D. & Suttles, J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J. Leukoc. Biol.76, 509–513 (2004). CASPubMed Google Scholar
Barnes, M. J. & Powrie, F. Regulatory T cells reinforce intestinal homeostasis. Immunity31, 401–411 (2009). CASPubMed Google Scholar
Varol, C. et al. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity31, 502–512 (2009). CASPubMed Google Scholar
Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature474, 298–306 (2011). CASPubMed Google Scholar
Jenkins, S. J. et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science332, 1284–1288 (2011). A study convincingly showing that tissue macrophages undergo rapidin situproliferation in response to IL-4. CASPubMedPubMed Central Google Scholar
Chen, G. Y. & Nunez, G. Sterile inflammation: sensing and reacting to damage. Nature Rev. Immunol.10, 826–837 (2010). CAS Google Scholar
Matzinger, P. & Kamala, T. Tissue-based class control: the other side of tolerance. Nature Rev. Immunol.11, 221–230 (2011). CAS Google Scholar
Nish, S. & Medzhitov, R. Host defense pathways: role of redundancy and compensation in infectious disease phenotypes. Immunity34, 629–636 (2011). An elegant exposition of the complexities associated with the understanding the host–pathogen interplay. CASPubMedPubMed Central Google Scholar
Borden, E. C. et al. Interferons at age 50: past, current and future impact on biomedicine. Nature Rev. Drug Discov.6, 975–990 (2007). CAS Google Scholar
Elinav, E., Strowig, T., Henao-Mejia, J. & Flavell, R. A. Regulation of the antimicrobial response by NLR proteins. Immunity34, 665–679 (2011). CASPubMed Google Scholar
Kawai, T. & Akira, S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity34, 637–650 (2011). CASPubMed Google Scholar
Osorio, F. & Reis, E. S. C. Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity34, 651–664 (2011). A concise up-to-date summary of the role of C-type lectin receptors in pathogen-specific immune responses. CASPubMed Google Scholar
Nathan, C. & Ding, A. Nonresolving inflammation. Cell140, 871–882 (2010). CASPubMed Google Scholar
Serbina, N. V., Jia, T., Hohl, T. M. & Pamer, E. G. Monocyte-mediated defense against microbial pathogens. Annu. Rev. Immunol.26, 421–452 (2008). CASPubMedPubMed Central Google Scholar
Haile, L. A. et al. Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology135, 871–881 (2008). CASPubMed Google Scholar
Garcia, M. R. et al. Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice. J. Clin. Invest.120, 2486–2496 (2010). CASPubMedPubMed Central Google Scholar
Delano, M. J. et al. MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis. J. Exp. Med.204, 1463–1474 (2007). CASPubMedPubMed Central Google Scholar
Semerad, C. L., Liu, F., Gregory, A. D., Stumpf, K. & Link, D. C. G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood. Immunity17, 413–423 (2002). CASPubMed Google Scholar
Semerad, C. L., Poursine-Laurent, J., Liu, F. & Link, D. C. A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation. Immunity11, 153–161 (1999). CASPubMed Google Scholar
Hanna, R. N. et al. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes. Nature Immunol.12, 778–785 (2011). An important study, which identified the orphan nuclear receptor NR4A1 as a master transcription factor that regulates the differentiation and survival of 'patrolling' LY6C−monocytes. CAS Google Scholar
Swirski, F. K. et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science325, 612–616 (2009). This study used a series of fascinating and technically challenging experiments to define the spleen as a monocyte reservoir. CASPubMedPubMed Central Google Scholar
Aldridge, J. R. Jr et al. TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc. Natl Acad. Sci. USA106, 5306–5311 (2009). CASPubMedPubMed Central Google Scholar
Dunay, I. R. & Sibley, L. D. Monocytes mediate mucosal immunity to Toxoplasma gondii. Curr. Opin. Immunol.22, 461–466 (2010). CASPubMedPubMed Central Google Scholar
Serbina, N. V. et al. Distinct responses of human monocyte subsets to Aspergillus fumigatus conidia. J. Immunol.183, 2678–2687 (2009). CASPubMed Google Scholar
Serbina, N. V. & Pamer, E. G. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nature Immunol.7, 311–317 (2006). CAS Google Scholar
Kim, Y. G. et al. The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes. Immunity34, 769–780 (2011). CASPubMedPubMed Central Google Scholar
Zhang, S., Kim, C. C., Batra, S., McKerrow, J. H. & Loke, P. Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. PLoS Negl. Trop. Dis.4, e648 (2010). PubMedPubMed Central Google Scholar
Goncalves, R., Zhang, X., Cohen, H., Debrabant, A. & Mosser, D. M. Platelet activation attracts a subpopulation of effector monocytes to sites of Leishmania major infection. J. Exp. Med.208, 1253–1265 (2011). A demonstration of a complex interaction between a parasite, platelets and local stimulation of CCL2 to draw monocytes to an infection site. CASPubMedPubMed Central Google Scholar
Shi, C. et al. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating Toll-like receptor ligands. Immunity34, 590–601 (2011). CASPubMedPubMed Central Google Scholar
Qian, B. Z. et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature475, 222–225 (2011). A fascinating study that identifies the origin of metastasis-associated macrophages, which promote the extravasation, seeding and growth of tumour cells. CASPubMedPubMed Central Google Scholar
Bosschaerts, T. et al. Tip-DC development during parasitic infection is regulated by IL-10 and requires CCL2/CCR2, IFN-γ and MyD88 signaling. PLoS Pathog.6, e1001045 (2010). PubMedPubMed Central Google Scholar
Hashimoto, D. et al. Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. J. Exp. Med.208, 1069–1082 (2011). CASPubMedPubMed Central Google Scholar
Denning, T. L., Wang, Y. C., Patel, S. R., Williams, I. R. & Pulendran, B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nature Immunol.8, 1086–1094 (2007). These authors identify an IL-10-producing population of CD11b+F4/80+CD11c−macrophages that promote the differentiation of FOXP3+ regulatory T cells and suppress TH17 cell responses. CAS Google Scholar
Zhu, B. et al. Plasticity of Ly-6Chi myeloid cells in T cell regulation. J. Immunol.187, 2418–2432 (2011). CASPubMed Google Scholar
Aziz, A., Soucie, E., Sarrazin, S. & Sieweke, M. H. MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science326, 867–871 (2009). This study showed that the transcription factors MAF and MAFB inhibit self-renewal of functionally differentiated monocytes and macrophages. CASPubMed Google Scholar
Pesce, J. T. et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog.5, e1000371 (2009). This study identifies ARG1 as the key mediator of the suppressive function of M2 macrophages. PubMedPubMed Central Google Scholar
Serbina, N. V., Salazar-Mather, T. P., Biron, C. A., Kuziel, W. A. & Pamer, E. G. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity19, 59–70 (2003). CASPubMed Google Scholar
Sindrilaru, A. et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J. Clin. Invest.121, 985–997 (2011). CASPubMedPubMed Central Google Scholar
Ricardo, S. D., van Goor, H. & Eddy, A. A. Macrophage diversity in renal injury and repair. J. Clin. Invest.118, 3522–3530 (2008). CASPubMedPubMed Central Google Scholar
Wynn, T. A. & Barron, L. Macrophages: master regulators of inflammation and fibrosis. Semin. Liver Dis.30, 245–257 (2010). CASPubMedPubMed Central Google Scholar
Wynn, T. A. Fibrotic disease and the TH1/TH2 paradigm. Nature Rev. Immunol.4, 583–594 (2004). CAS Google Scholar
Xiao, W., Hong, H., Kawakami, Y., Lowell, C. A. & Kawakami, T. Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn/Hck, SHIP, and Stat5. J. Clin. Invest.118, 924–934 (2008). CASPubMedPubMed Central Google Scholar
Biswas, S. K. & Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nature Immunol.11, 889–896 (2010). CAS Google Scholar
Arnold, L. et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med.204, 1057–1069 (2007). CASPubMedPubMed Central Google Scholar
Barron, L. & Wynn, T. A. Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages. Am. J. Physiol. Gastrointest. Liver Physiol.300, G723–G728 (2011). CASPubMedPubMed Central Google Scholar
Roberts, A. B. et al. Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl Acad. Sci. USA83, 4167–4171 (1986). CASPubMedPubMed Central Google Scholar
Sunderkotter, C., Steinbrink, K., Goebeler, M., Bhardwaj, R. & Sorg, C. Macrophages and angiogenesis. J. Leukoc. Biol.55, 410–422 (1994). CASPubMed Google Scholar
Shimokado, K. et al. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell43, 277–286 (1985). CASPubMed Google Scholar
Atabai, K. et al. Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J. Clin. Invest.119, 3713–3722 (2009). CASPubMedPubMed Central Google Scholar
Curiel, T. J. et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Med.10, 942–949 (2004). CASPubMed Google Scholar
Imai, T. et al. Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int. Immunol.11, 81–88 (1999). CASPubMed Google Scholar
Gabbiani, G. The myofibroblast in wound healing and fibrocontractive diseases. J. Pathol.200, 500–503 (2003). CASPubMed Google Scholar
Fiorentino, D. F. et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J. Immunol.146, 3444–3451 (1991). CASPubMed Google Scholar
Savage, N. D. et al. Human anti-inflammatory macrophages induce Foxp3+ GITR+ CD25+ regulatory T cells, which suppress via membrane-bound TGFβ-1. J. Immunol.181, 2220–2226 (2008). CASPubMed Google Scholar
Herbert, D. R. et al. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J. Immunol.184, 6438–6446 (2010). CASPubMed Google Scholar
Sutherland, T. E., Maizels, R. M. & Allen, J. E. Chitinases and chitinase-like proteins: potential therapeutic targets for the treatment of T-helper type 2 allergies. Clin. Exp. Allergy39, 943–955 (2009). CASPubMed Google Scholar
Pesce, J. T. et al. Retnla (Relmα/Fizz1) suppresses helminth-induced Th2-type immunity. PLoS Pathog.5, e1000393 (2009). PubMedPubMed Central Google Scholar
Reese, T. A. et al. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature447, 92–96 (2007). CASPubMedPubMed Central Google Scholar
London, A. et al. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med.208, 23–39 (2011). CASPubMedPubMed Central Google Scholar
Odegaard, J. I. & Chawla, A. Alternative macrophage activation and metabolism. Annu. Rev. Pathol.6, 275–297 (2011). CASPubMedPubMed Central Google Scholar
Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest.117, 175–184 (2007). This study, along with reference 84, shows that diet-induced obesity can lead to a shift in the activation state of adipose-associated macrophages from an M2 phenotype (induced by PPARγ) in lean animals to an M1 phenotype that contributes to insulin resistance. CASPubMedPubMed Central Google Scholar
Odegaard, J. I. et al. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature447, 1116–1120 (2007). CASPubMedPubMed Central Google Scholar
Vandanmagsar, B. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature Med.17, 179–188 (2011). CASPubMed Google Scholar
Chawla, A. et al. Macrophage-mediated inflammation in metabolic disease. Nature Rev. Immunol. 10 Oct 2011 (doi:10.1038/nri3071). CASPubMedPubMed Central Google Scholar
de Waal Malefyt, R. et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J. Immunol.151, 6370–6381 (1993). CASPubMed Google Scholar
Gordon, S. Alternative activation of macrophages. Nature Rev. Immunol.3, 23–35 (2003). CAS Google Scholar
Anthony, R. M. et al. Memory TH2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nature Med.12, 955–960 (2006). CASPubMed Google Scholar
Bhatia, S. et al. Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype. PLoS ONE6, e15943 (2011). CASPubMedPubMed Central Google Scholar
Prasse, A. et al. IL-10-producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients. J. Allergy Clin. Immunol.119, 464–471 (2007). CASPubMed Google Scholar
Kim, E. Y. et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nature Med.14, 633–640 (2008). CASPubMed Google Scholar
Nagarkar, D. R. et al. Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages. J. Immunol.185, 2525–2535 (2010). CASPubMed Google Scholar
Stolarski, B., Kurowska-Stolarska, M., Kewin, P., Xu, D. & Liew, F. Y. IL-33 exacerbates eosinophil-mediated airway inflammation. J. Immunol.185, 3472–3480 (2010). CASPubMed Google Scholar
Kurowska-Stolarska, M. et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J. Immunol.183, 6469–6477 (2009). CASPubMed Google Scholar
van Rijt, L. S. et al. In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. J. Exp. Med.201, 981–991 (2005). CASPubMedPubMed Central Google Scholar
Shirey, K. A. et al. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4Rα-, TLR4-, and IFN-β-dependent. Mucosal Immunol.3, 291–300 (2010). CASPubMedPubMed Central Google Scholar
Nair, M. G. et al. Alternatively activated macrophage-derived RELM-α is a negative regulator of type 2 inflammation in the lung. J. Exp. Med.206, 937–952 (2009). CASPubMedPubMed Central Google Scholar
Sica, A. & Bronte, V. Altered macrophage differentiation and immune dysfunction in tumor development. J. Clin. Invest.117, 1155–1166 (2007). CASPubMedPubMed Central Google Scholar
Andreu, P. et al. FcRγ activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell17, 121–134 (2010). CASPubMedPubMed Central Google Scholar
de Visser, K. E., Korets, L. V. & Coussens, L. M. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell7, 411–423 (2005). CASPubMed Google Scholar
Nardin, A. & Abastado, J. P. Macrophages and cancer. Front. Biosci.13, 3494–3505 (2008). CASPubMed Google Scholar
Yang, X. D. et al. Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells. Nature Med.17, 87–95 (2011). CASPubMed Google Scholar
Sierra, J. R. et al. Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages. J. Exp. Med.205, 1673–1685 (2008). CASPubMedPubMed Central Google Scholar
Kryczek, I. et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J. Exp. Med.203, 871–881 (2006). CASPubMedPubMed Central Google Scholar
Imtiyaz, H. Z. et al. Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation. J. Clin. Invest.120, 2699–2714 (2010). CASPubMedPubMed Central Google Scholar
Steidl, C. et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N. Engl. J. Med.362, 875–885 (2010). CASPubMedPubMed Central Google Scholar
Ahn, G. O. et al. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc. Natl Acad. Sci. USA107, 8363–8368 (2010). CASPubMedPubMed Central Google Scholar
DeNardo, D. G. et al. CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell16, 91–102 (2009). CASPubMedPubMed Central Google Scholar
Terabe, M. et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R–STAT6 pathway. Nature Immunol.1, 515–520 (2000). CAS Google Scholar
Gocheva, V. et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev.24, 241–255 (2010). CASPubMedPubMed Central Google Scholar
Sinha, P., Clements, V. K. & Ostrand-Rosenberg, S. Interleukin-13-regulated M2 macrophages in combination with myeloid suppressor cells block immune surveillance against metastasis. Cancer Res.65, 11743–11751 (2005). CASPubMed Google Scholar
Zorro Manrique, S. et al. Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth. J. Exp. Med. 13 Jun 2011 (doi:10.1084/jem.20100730). This study identified FOXP3 expression in a subset of macrophages; this macrophage subset exhibits a distinct gene expression profile and may contribute to immunoregulation. PubMed Central Google Scholar
Duluc, D. et al. Interferon-γ reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. Int. J. Cancer125, 367–373 (2009). CASPubMed Google Scholar
Fong, C. H. et al. An antiinflammatory role for IKKβ through the inhibition of “classical” macrophage activation. J. Exp. Med.205, 1269–1276 (2008). This study identified a new role for inhibitor of NF-κB kinase-β (IKKβ) in the regulation of macrophage activation by showing that deletion of IKKβ in the myeloid lineage confers resistance to infection with group BStreptococcusthrough increased production of IL-12, iNOS and MHC class II by macrophages. CASPubMedPubMed Central Google Scholar
Song, L. et al. Vα24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J. Clin. Invest.119, 1524–1536 (2009). CASPubMedPubMed Central Google Scholar
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell144, 646–674 (2011). CASPubMed Google Scholar
Murphy, C. A. et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med.198, 1951–1957 (2003). CASPubMedPubMed Central Google Scholar
Smith, A. M. et al. Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. J. Exp. Med.206, 1883–1897 (2009). CASPubMedPubMed Central Google Scholar
Kawane, K. et al. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature443, 998–1002 (2006). CASPubMed Google Scholar
Platt, A. M., Bain, C. C., Bordon, Y., Sester, D. P. & Mowat, A. M. An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J. Immunol.184, 6843–6854 (2010). CASPubMed Google Scholar
Kamada, N. et al. Human CD14+ macrophages in intestinal lamina propria exhibit potent antigen-presenting ability. J. Immunol.183, 1724–1731 (2009). CASPubMed Google Scholar
Kamada, N. et al. Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. J. Clin. Invest.118, 2269–2280 (2008). CASPubMedPubMed Central Google Scholar
Smith, P. D. et al. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol.4, 31–42 (2011). PubMed Google Scholar
Murai, M. et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nature Immunol.10, 1178–1184 (2009). CAS Google Scholar
Gelderman, K. A. et al. Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species. J. Clin. Invest.117, 3020–3028 (2007). CASPubMedPubMed Central Google Scholar
Hendriks, J. J., Teunissen, C. E., de Vries, H. E. & Dijkstra, C. D. Macrophages and neurodegeneration. Brain Res. Brain Res. Rev.48, 185–195 (2005). CASPubMed Google Scholar
Huang, D. R., Wang, J., Kivisakk, P., Rollins, B. J. & Ransohoff, R. M. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J. Exp. Med.193, 713–726 (2001). CASPubMedPubMed Central Google Scholar
Codarri, L. et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nature Immunol.12, 560–567 (2011). CAS Google Scholar
El-Behi, M. et al. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nature Immunol.12, 568–575 (2011). CAS Google Scholar
Ponomarev, E. D., Veremeyko, T., Barteneva, N., Krichevsky, A. M. & Weiner, H. L. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α–PU.1 pathway. Nature Med.17, 64–70 (2011). This study identified miR-124 both as a key regulator of microglia quiescence in the central nervous system and as a previously unknown modulator of monocyte and macrophage activation. CASPubMed Google Scholar
Kiefer, R., Kieseier, B. C., Stoll, G. & Hartung, H. P. The role of macrophages in immune-mediated damage to the peripheral nervous system. Prog. Neurobiol.64, 109–127 (2001). CASPubMed Google Scholar
Hoek, R. M. et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science290, 1768–1771 (2000). CASPubMed Google Scholar
Shechter, R. et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med.6, e1000113 (2009). PubMedPubMed Central Google Scholar
Woollard, K. J. & Geissmann, F. Monocytes in atherosclerosis: subsets and functions. Nature Rev. Cardiol.7, 77–86 (2010). Google Scholar
Li, A. C. & Glass, C. K. The macrophage foam cell as a target for therapeutic intervention. Nature Med.8, 1235–1242 (2002). CASPubMed Google Scholar
Febbraio, M., Hajjar, D. P. & Silverstein, R. L. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J. Clin. Invest.108, 785–791 (2001). CASPubMedPubMed Central Google Scholar
Acton, S. et al. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science271, 518–520 (1996). CASPubMed Google Scholar
Suzuki, H. et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature386, 292–296 (1997). CASPubMed Google Scholar
Pinderski, L. J. et al. Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient mice by altering lymphocyte and macrophage phenotypes. Circ. Res.90, 1064–1071 (2002). CASPubMed Google Scholar
Smith, J. D. et al. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc. Natl Acad. Sci. USA92, 8264–8268 (1995). CASPubMedPubMed Central Google Scholar
Stoneman, V. et al. Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques. Circ. Res.100, 884–893 (2007). CASPubMedPubMed Central Google Scholar
Park, Y. M., Febbraio, M. & Silverstein, R. L. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima. J. Clin. Invest.119, 136–145 (2009). CASPubMed Google Scholar
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J. & Glass, C. K. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature391, 79–82 (1998). CASPubMed Google Scholar
Erbay, E. et al. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nature Med.15, 1383–1391 (2009). CASPubMed Google Scholar
Nagaoka, I., Trapnell, B. C. & Crystal, R. G. Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis. J. Clin. Invest.85, 2023–2027 (1990). CASPubMedPubMed Central Google Scholar
Nagaoka, I., Trapnell, B. C. & Crystal, R. G. Regulation of insulin-like growth factor I gene expression in the human macrophage-like cell line U937. J. Clin. Invest.85, 448–455 (1990). CASPubMedPubMed Central Google Scholar
Broekelmann, T. J., Limper, A. H., Colby, T. V. & McDonald, J. A. Transforming growth factor β1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc. Natl Acad. Sci. USA88, 6642–6646 (1991). CASPubMedPubMed Central Google Scholar
Kolb, M., Margetts, P. J., Anthony, D. C., Pitossi, F. & Gauldie, J. Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis. J. Clin. Invest.107, 1529–1536 (2001). CASPubMedPubMed Central Google Scholar
Gasse, P. et al. IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. J. Clin. Invest.117, 3786–3799 (2007). CASPubMedPubMed Central Google Scholar
Wilson, M. S. et al. Bleomycin and IL-1β-mediated pulmonary fibrosis is IL-17A dependent. J. Exp. Med.207, 535–552 (2010). CASPubMedPubMed Central Google Scholar
Martinez, F. O., Sica, A., Mantovani, A. & Locati, M. Macrophage activation and polarization. Front. Biosci.13, 453–461 (2008). CASPubMed Google Scholar
Lee, C. G. et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1 . J. Exp. Med.194, 809–821 (2001). CASPubMedPubMed Central Google Scholar
Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest.115, 56–65 (2005). CASPubMedPubMed Central Google Scholar
Wilson, M. S. et al. IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J. Clin. Invest.117, 2941–2951 (2007). CASPubMedPubMed Central Google Scholar
Aouadi, M. et al. Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature458, 1180–1184 (2009). CASPubMedPubMed Central Google Scholar
Krausgruber, T. et al. IRF5 promotes inflammatory macrophage polarization and TH1–TH17 responses. Nature Immunol.12, 231–238 (2011). These authors show that IRF5 expression in macrophages is reversibly induced by inflammatory stimuli and contributes to the plasticity of macrophage polarization, thus identifying IRF5 as a transcriptional repressor. CAS Google Scholar
Bogdan, C. Species differences in macrophage NO production are important. Nature Immunol.3, 102 (2002). CAS Google Scholar
Fang, F. C. & Nathan, C. F. Man is not a mouse: reply. J. Leukoc. Biol.81, 580 (2007). CASPubMed Google Scholar
Nathan, C. Role of iNOS in human host defense. Science312, 1874–1875; author reply 1874–1875 (2006). CASPubMed Google Scholar
Manicassamy, S. et al. Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science329, 849–853 (2010). CASPubMedPubMed Central Google Scholar
Murphy, K. M. Comment on “Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine”. Science333, 405; author reply 405 (2011). PubMed Google Scholar
Denning, T. L. et al. Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory t cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J. Immunol.187, 733–747 (2011). CASPubMed Google Scholar
Hume, D. A. Macrophages as APC and the dendritic cell myth. J. Immunol.181, 5829–5835 (2008). CASPubMed Google Scholar
Asano, K. et al. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity34, 85–95 (2011). CASPubMed Google Scholar
Hamann, J. et al. EMR1, the human homolog of F4/80, is an eosinophil-specific receptor. Eur. J. Immunol.37, 2797–2802 (2007). CASPubMed Google Scholar
Liao, X. et al. Kruppel-like factor 4 regulates macrophage polarization. J. Clin. Invest.121, 2736–2749 (2011). This paper identified Krüppel-like factor 4 (KLF4) as a crucial regulator of macrophage polarization. KLF4 cooperates with STAT6 to induce M2 and inhibit M1 macrophage activation via sequestration of co-activators required for NF-κB activation. CASPubMedPubMed Central Google Scholar
El Kasmi, K. C. et al. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nature Immunol.9, 1399–1406 (2008). These authors identify a novel TLR-dependent pathway for the induction of ARG1 expression in mouse macrophages that leads to decreased NO production and increased susceptibility to intracellular infections. CAS Google Scholar
Qualls, J. E. et al. Arginine usage in mycobacteria-infected macrophages depends on autocrine-paracrine cytokine signaling. Sci. Signal.3, ra62 (2010). PubMedPubMed Central Google Scholar
Saraiva, M. & O'Garra, A. The regulation of IL-10 production by immune cells. Nature Rev. Immunol.10, 170–181 (2010). CAS Google Scholar
Shirey, K. A., Cole, L. E., Keegan, A. D. & Vogel, S. N. Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism. J. Immunol.181, 4159–4167 (2008). CASPubMed Google Scholar
Wu, D. et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science332, 243–247 (2011). CASPubMedPubMed Central Google Scholar