Macrophage biology in development, homeostasis and disease (original) (raw)
Gautier, E. L. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nature Immunol.13, 1118–1128 (2012)This paper provides a detailed analysis of the macrophage transcriptome. Several novel genes are identified that are distinctly and universally associated with mature tissue-resident macrophages, but the results also illustrate the extreme diversity of these cell types. ArticleCAS Google Scholar
Gordon, S. Alternative activation of macrophages. Nature Rev. Immunol.3, 23–35 (2003) ArticleCAS 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)This paper shows that tissue macrophages can proliferate in response to IL-4, suggesting that monocyte recruitment and definitive haematopoiesis may not be required for macrophage expansion in type 2 immunity. ArticleADSCASPubMedPubMed Central Google Scholar
Schulz, C. et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science336, 86–90 (2012)Together withrefs 10and11, this paper indicates that the mononuclear phagocytic lineage needs to be reassessed and that most resident adult macrophage populations derive from the yolk sac. ArticleADSCASPubMed Google Scholar
Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nature Rev. Immunol.11, 723–737 (2011) ArticleCAS Google Scholar
Wynn, T. A. & Barron, L. Macrophages: master regulators of inflammation and fibrosis. Semin. Liver Dis.30, 245–257 (2010)A comprehensive review examining the regulatory role of macrophages in chronic inflammatory disease and fibrosis. ArticleCASPubMedPubMed Central Google Scholar
Gordon, S. & Taylor, P. R. Monocyte and macrophage heterogeneity. Nature Rev. Immunol.5, 953–964 (2005)The definitive review of activated and alternatively activated macrophages, with detailed explanations of the definitions and restrictions of these terms. ArticleCAS Google Scholar
Hoeffel, G. et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med.209, 1167–1181 (2012) ArticleCASPubMedPubMed Central Google Scholar
Frankenberger, M. et al. A defect of CD16-positive monocytes can occur without disease. Immunobiology218, 169–174 (2013) ArticleCASPubMed Google Scholar
Hume, D. A. Macrophages as APC and the dendritic cell myth. J. Immunol.181, 5829–5835 (2008) ArticleCASPubMed Google Scholar
Satpathy, A. T., Wu, X., Albring, J. C. & Murphy, K. M. Re(de)fining the dendritic cell lineage. Nature Immunol.13, 1145–1154 (2012) ArticleCAS Google Scholar
Chitu, V. & Stanley, E. R. Colony-stimulating factor-1 in immunity and inflammation. Curr. Opin. Immunol.18, 39–48 (2006) ArticleCASPubMed Google Scholar
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K. & Pollard, J. W. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS ONE6, e26317 (2011) ArticleADSCASPubMedPubMed Central Google Scholar
Wei, S. et al. Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. J. Leukoc. Biol.8, 495–505 (2010) ArticleCAS Google Scholar
Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nature Immunol.13, 753–760 (2012) ArticleCAS Google Scholar
Pollard, J. W. Trophic macrophages in development and disease. Nature Rev. Immunol.9, 259–270 (2009) ArticleCAS Google Scholar
Niida, S. et al. Vascular endothelial growth factor can substitute for macrophage colony-stimulating dactor in the support of osteoclastic bone resorption. J. Exp. Med.190, 293–298 (1999) ArticleCASPubMedPubMed Central Google Scholar
Hamilton, J. A. & Achuthan, A. Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol.34, 81–89 (2013) ArticleCASPubMed Google Scholar
Miller, J. C. et al. Deciphering the transcriptional network of the dendritic cell lineage. Nature Immunol.13, 888–899 (2012) ArticleCAS Google Scholar
Hume, D. A. The complexity of constitutive and inducible gene expression in mononuclear phagocytes. J. Leukoc. Biol. (2012)
Edwards, J. R. & Mundy, G. R. Advances in osteoclast biology: old findings and new insights from mouse models. Nature Rev. Rheumatol.7, 235–243 (2011) ArticleCAS Google Scholar
Stefater, J. A., III, Ren, S., Lang, R. A. & Duffield, J. S. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends Mol. Med. (2011)
Gyorki, D. E., Asselin-Labat, M. L., van Rooijen, N., Lindeman, G. J. & Visvader, J. E. Resident macrophages influence stem cell activity in the mammary gland. Breast Cancer Res.11, R62 (2009) ArticlePubMedPubMed Central Google Scholar
Pull, S. L., Doherty, J. M., Mills, J. C., Gordon, J. I. & Stappenbeck, T. S. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc. Natl Acad. Sci. USA102, 99–104 (2005) ArticleADSCASPubMed Google Scholar
Chow, A. et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J. Exp. Med.208, 261–271 (2011)This paper, together withrefs 27, 28and30, shows that macrophages regulate various stem cell niches. ArticleCASPubMedPubMed Central Google Scholar
Boulter, L. et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nature Med.18, 572–579 (2012) ArticleADSCASPubMed Google Scholar
Kawane, K. et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science292, 1546–1549 (2001) ArticleADSCASPubMed Google Scholar
Jaiswal, S. et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell138, 271–285 (2009) ArticleCASPubMedPubMed Central Google Scholar
Gordy, C., Pua, H., Sempowski, G. D. & He, Y. W. Regulation of steady-state neutrophil homeostasis by macrophages. Blood117, 618–629 (2011) ArticleCASPubMedPubMed Central Google Scholar
Dai, X. M. et al. Targeted disruption of the mouse CSF-1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primititive progenitor cell frequencies and reproductive defects. Blood99, 111–120 (2002) ArticleCASPubMed Google Scholar
Savill, J., Dransfield, I., Gregory, C. & Haslett, C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nature Rev. Immunol.2, 965–975 (2002) ArticleCAS Google Scholar
Rao, S. et al. Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch. Development134, 4449–4458 (2007) ArticleCASPubMed Google Scholar
Stefater, J. A., III et al. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature474, 511–515 (2011)An important paper showing the molecular basis of the macrophage regulation of angiogenesis through the WNT pathway. ArticleCASPubMedPubMed Central Google Scholar
Tammela, T. et al. VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nature Cell Biol.13, 1202–1213 (2011) ArticleCASPubMed Google Scholar
Fantin, A. et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood116, 829–840 (2010) ArticleCASPubMedPubMed Central Google Scholar
Gordon, E. J. et al. Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation. Development137, 3899–3910 (2010) ArticleCASPubMedPubMed Central Google Scholar
Machnik, A. et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nature Med.15, 545–552 (2009) ArticleCASPubMed Google Scholar
Nandi, S. et al. The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation. Dev. Biol.367, 100–113 (2012) ArticleCASPubMedPubMed Central Google Scholar
Li, Y., Du, X. F., Liu, C. S., Wen, Z. L. & Du, J. L. Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo. Dev. Cell23, 1189–1202 (2012)A paper that demonstrates that microglia regulate neuronal activity in zebrafish using intravital imaging. ArticleCASPubMed Google Scholar
Paolicelli, R. C. et al. Synaptic pruning by microglia is necessary for normal brain development. Science333, 1456–1458 (2011) ArticleADSCASPubMed Google Scholar
Rademakers, R. et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nature Genet.44, 200–205 (2011) ArticlePubMedCAS 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) ArticleCASPubMedPubMed Central Google Scholar
Kigerl, K. A. et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J. Neurosci.29, 13435–13444 (2009) ArticleCASPubMedPubMed Central Google Scholar
Salegio, E. A., Pollard, A. N., Smith, M. & Zhou, X. F. Macrophage presence is essential for the regeneration of ascending afferent fibres following a conditioning sciatic nerve lesion in adult rats. BMC Neurosci.12, 11 (2011) ArticlePubMed Google Scholar
Chawla, A., Nguyen, K. D. & Goh, Y. P. Macrophage-mediated inflammation in metabolic disease. Nature Rev. Immunol.11, 738–749 (2011) ArticleCAS 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) ArticleCASPubMedPubMed Central Google Scholar
Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest.112, 1821–1830 (2003)This paper, together withref. 55, was the first to demonstrate that obesity results in infiltration of WAT by macrophages, which contributes to its inflamed nature. ArticleCASPubMedPubMed Central Google Scholar
Kang, K. et al. Adipocyte-derived Th2 cytokines and myeloid PPARδ regulate macrophage polarization and insulin sensitivity. Cell Metab.7, 485–495 (2008) ArticleCASPubMedPubMed Central Google Scholar
Odegaard, J. I. et al. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature447, 1116–1120 (2007)This paper showed that residence of AAMs in WAT is necessary for the maintenance of insulin sensitivity in obese animals. ArticleADSCASPubMedPubMed Central Google Scholar
Odegaard, J. I. et al. Alternative M2 activation of Kupffer cells by PPAR_δ_ ameliorates obesity-induced insulin resistance. Cell Metab.7, 496–507 (2008) ArticleCASPubMedPubMed Central Google Scholar
Wu, D. et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 332, 243–247 (2011)
Weisberg, S. P. et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest.116, 115–124 (2006) ArticleCASPubMed Google Scholar
Cinti, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res.46, 2347–2355 (2005) ArticleCASPubMed Google Scholar
Lowell, B. B. & Spiegelman, B. M. Towards a molecular understanding of adaptive thermogenesis. Nature404, 652–660 (2000) ArticleCASPubMed Google Scholar
Nguyen, K. D. et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature480, 104–108 (2011)This paper demonstrated a physiological function for AAMs in sustaining adaptive thermogenesis, which allows mammals to adapt to cold environments. ArticleADSCASPubMedPubMed Central Google Scholar
Huang, W. et al. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes59, 347–357 (2010) ArticleCASPubMed Google Scholar
Eguchi, K. et al. Saturated fatty acid and TLR signaling link beta cell dysfunction and islet inflammation. Cell Metab.15, 518–533 (2012) ArticleCASPubMed Google Scholar
Ehses, J. A. et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes56, 2356–2370 (2007) ArticleCASPubMed 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) ArticleCAS Google Scholar
Krausgruber, T. et al. IRF5 promotes inflammatory macrophage polarization and TH1–TH17 responses. Nature Immunol.12, 231–238 (2011)This paper showed that IRF5 expression is induced in macrophages in response to inflammatory stimuli and that this contributes to the polarization of macrophages with an inflammatory phenotype, which causes TH1 and TH17 cells to respond. ArticleCAS 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) ArticleADSCASPubMedPubMed Central Google Scholar
Balkwill, F. R. & Mantovani, A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin. Cancer Biol.22, 33–40 (2012) ArticleCASPubMed Google Scholar
Deng, L. et al. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis. Am. J. Pathol.176, 952–967 (2010) ArticleCASPubMedPubMed Central Google Scholar
DeNardo, D. G., Andreu, P. & Coussens, L. M. Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev.29, 309–316 (2010) ArticlePubMedPubMed Central Google Scholar
Hanahan, D. & Coussens, L. M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell21, 309–322 (2012) ArticleCASPubMed Google Scholar
Condeelis, J. & Pollard, J. W. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell124, 263–266 (2006) ArticleCASPubMed Google Scholar
Lin, E. Y. et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res.66, 11238–11246 (2006) ArticleCASPubMed Google Scholar
Mazzieri, R. et al. Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell19, 512–526 (2011) ArticleCASPubMed Google Scholar
Murdoch, C., Muthana, M., Coffelt, S. B. & Lewis, C. E. The role of myeloid cells in the promotion of tumour angiogenesis. Nature Rev. Cancer8, 618–631 (2008) ArticleCAS Google Scholar
Shojaei, F. et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nature Biotechnol.25, 911–920 (2007) ArticleCAS Google Scholar
Du, R. et al. HIF1α induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell13, 206–220 (2008) ArticleCASPubMedPubMed Central Google Scholar
Lin, E. Y. et al. Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages. Mol. Oncol.1, 288–302 (2007) ArticlePubMedPubMed Central Google Scholar
Psaila, B. & Lyden, D. The metastatic niche: adapting the foreign soil. Nature Rev. Cancer9, 285–293 (2009) ArticleCAS Google Scholar
Peinado, H. et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Med.18, 883–891 (2012) ArticleCASPubMed Google Scholar
Gil-Bernabé, A. M. et al. Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood119, 3164–3175 (2012) ArticlePubMedCAS Google Scholar
Qian, B. Z. et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature475, 222–225 (2011)This paper suggests that macrophages may represent a therapeutic target to prevent tumour cell metastatic seeding and growth. ArticleCASPubMedPubMed Central Google Scholar
Wu, Y. & Zheng, L. Dynamic education of macrophages in different areas of human tumors. Cancer Microenvironment5, 195–201 (2012) ArticlePubMedPubMed Central Google Scholar
Pello, O. M. et al. Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood119, 411–421 (2012) ArticlePubMedCAS Google Scholar
Zabuawala, T. et al. An ets2-driven transcriptional program in tumor-associated macrophages promotes tumor metastasis. Cancer Res.70, 1323–1333 (2010) ArticleCASPubMedPubMed Central Google Scholar
Hansson, G. K. & Hermansson, A. The immune system in atherosclerosis. Nature Immunol.12, 204–212 (2011) ArticleCAS 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
Libby, P., Ridker, P. M. & Hansson, G. K. Progress and challenges in translating the biology of atherosclerosis. Nature473, 317–325 (2011) ArticleADSCASPubMed Google Scholar
Julia, V. et al. A restricted subset of dendritic cells captures airborne antigens and remains able to activate specific T cells long after antigen exposure. Immunity16, 271–283 (2002) ArticleCASPubMed Google Scholar
Ford, A. Q. et al. Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation. BMC Immunol.13, 6 (2012) ArticleCASPubMedPubMed Central Google Scholar
Moreira, A. P. et al. Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease. J. Allergy Clin. Immunol.126, 712–721 (2010) ArticleCASPubMed Google Scholar
Melgert, B. N. et al. More alternative activation of macrophages in lungs of asthmatic patients. J. Allergy Clin. Immunol.127, 831–833 (2011) ArticlePubMed Google Scholar
Nieuwenhuizen, N. E. et al. Allergic airway disease is unaffected by the absence of IL-4Rα-dependent alternatively activated macrophages. J. Allergy Clin. Immunol.130, 743–750 (2012) ArticleCASPubMed Google Scholar
Murray, P. J. & Wynn, T. A. Obstacles and opportunities for understanding macrophage polarization. J. Leukoc. Biol.89, 557–563 (2011) ArticleCAS 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) ArticleCASPubMed 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) ArticleCASPubMed Google Scholar
Rivollier, A., He, J., Kole, A., Valatas, V. & Kelsall, B. L. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J. Exp. Med.209, 139–155 (2012) ArticleCASPubMedPubMed Central 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) ArticleCASPubMedPubMed 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) ArticleCASPubMedPubMed Central 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) ArticleCAS Google Scholar
Hoek, R. M. et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science290, 1768–1771 (2000) ArticleADSCASPubMed 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) ArticlePubMedPubMed CentralCAS 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) ArticleCASPubMedPubMed Central Google Scholar
Wynn, T. A. & Ramalingam, T. R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nature Med.18, 1028–1040 (2012) ArticleCASPubMed Google Scholar
Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol. 8, 958–969 (2008)
Thomas, J. A. et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology53, 2003–2015 (2011) ArticleCASPubMed Google Scholar
Ravasi, T. et al. An atlas of combinatorial transcriptional regulation in mouse and man. Cell. 140, 744–752 (2010)
Frankenberger, M. et al. Transcript profiling of CD16-positive monocytes reveals a unique molecular fingerprint. Eur. J. Immunol.42, 957–974 (2012) ArticleCASPubMed Google Scholar
Entenberg, D. et al. Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging. Nature Protocols6, 1500–1520 (2011) ArticleCASPubMedPubMed Central Google Scholar