Embryonic and Adult-Derived Resident Cardiac Macrophages Are Maintained through Distinct Mechanisms at Steady State and during Inflammation
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Cardiac macrophages are crucial for tissue repair after cardiac injury but are not well characterized. Here we identify four populations of cardiac macrophages. At steady state, resident macrophages were primarily maintained through local proliferation. However, after macrophage depletion or during cardiac inflammation, Ly6c(hi) monocytes contributed to all four macrophage populations, whereas resident macrophages also expanded numerically through proliferation. Genetic fate mapping revealed that yolk-sac and fetal monocyte progenitors gave rise to the majority of cardiac macrophages, and the heart was among a minority of organs in which substantial numbers of yolk-sac macrophages persisted in adulthood. CCR2 expression and dependence distinguished cardiac macrophages of adult monocyte versus embryonic origin. Transcriptional and functional data revealed that monocyte-derived macrophages coordinate cardiac inflammation, while playing redundant but lesser roles in antigen sampling and efferocytosis. These data highlight the presence of multiple cardiac macrophage subsets, with different functions, origins, and strategies to regulate compartment size.
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During experimental autoimmune myocarditis (EAM), a significant increase in pro-inflammatory Ly6Chi monocytes and recruited CCR2+ macrophages is observed throughout the cardiac tissue.
“During the course of experimental autoimmune myocarditis (EAM), a significant increase in the number of pro-inflammatory Ly6Chi monocytes and recruited CCR2+ macrophages is observed throughout the cardiac tissue [7,8,10].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
The Results sections on cardiac macrophage expansion report Ly6chi monocyte influx and expansion of macrophage populations during angiotensin II infusion, including recruitment contributing to CCR2+ macrophages. They do not report these changes during experimental autoimmune myocarditis or establish that the increase occurs throughout cardiac tissue; searches for EAM and myocarditis found no such passage. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMyeloid clusters 1 and 5 highly expressed Ccr2, a marker of monocyte-derived macrophages that enter from the circulation.
“Clusters 1 and 5 had high expression of Ccr2, a marker of monocyte-derived macrophages that infiltrate from the circulation17-19 (Fig. 1J and Extended Data Fig. 1C-E).”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [18]
Macrophages constitute a highly heterogeneous cell population and are key mediators in both maintaining homeostasis and the pathogenesis of myocardial injury.
“Macrophages, which constitute a highly heterogeneous cell population, are key mediators in both maintaining homeostasis and the pathogenesis of myocardial injury [7,8].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
In the heart, two main lineages of macrophages with distinct origins and functions are distinguished: tissue-resident macrophages (TRMs; typically CCR2-), predominantly derived from embryonic development, and recruited monocyte-derived macrophages (CCR2+), which infiltrate from the bloodstream in response to injury.
“In the heart, two main lineages of macrophages with distinct origins and functions are distinguished: tissue-resident macrophages (TRMs; typically CCR2-), predominantly derived from embryonic development, and recruited monocyte-derived macrophages (CCR2+), which infiltrate from the bloodstream in response to injury [7,8,9,10].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
Species-specific differences in macrophage ontogeny, cytokine networks, and the composition of the cardiac immune niche may limit direct extrapolation of findings.
“Species-specific differences in macrophage ontogeny, cytokine networks, and the composition of the cardiac immune niche may limit direct extrapolation of findings [7].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [7]
The Results describe cardiac macrophage origins and inflammatory functions in mice, and the Experimental Procedures identify the animals studied as mice (page unavailable). Our copy does not compare species or discuss whether differences in ontogeny, cytokine networks, or the cardiac immune niche limit extrapolation; searches for human–mouse differences and extrapolation found no such passage. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Microglia in the developing brain proliferate locally at a low rate and are not normally replaced by other monocytes and macrophages from outside the brain, unlike most other tissue-resident macrophages.
“Microglia in the developing brain proliferate locally at a low rate and are not normally replaced by other monocytes and macrophages from outside the brain, in contrast to most other tissue-resident macrophages (which also initially originate from yolk sac-derived macrophages, but are partially or fully replaced by fetal liver- or blood monocyte-derived macrophages [Bain et al., 2014, Calderon et”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Epelman et al., 2014
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Cites
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · see citing works
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245 · see citing works
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
Qian, B.-Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., Kaiser, E. A., Snyder, L. A., & Pollard, J. W. (2011) · Nature · doi:10.1038/nature10138 · Cited by 2,874 · see citing works
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578 · see citing works
Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M. B., Leboeuf, M., Becker, C. D., See, P., Price, J., Lucas, D., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.004 · Cited by 2,311 · cited 3× · see citing works
“transplanted monocytes, indicating local macrophage expansion in these niches despite genotoxic injury (Hashimoto et al., 2013).”
BackgroundResultInfluentialSelf-citationNahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300 · see citing works
the Immunological Genome Consortium, Gautier, E. L., Shay, T., Miller, J., Greter, M., Jakubzick, C., Ivanov, S., Helft, J., Chow, A., Elpek, K. G., et al. (2012) · Nature Immunology · doi:10.1038/ni.2419 · Cited by 1,972 · see citing works
Self-citationSerbina, N. V., & Pamer, E. G. (2006) · Nature Immunology · doi:10.1038/ni1309 · Cited by 1,658 · see citing works
Jenkins, S., Ruckerl, D., Cook, P., Jones, L., Finkelman, F., van Rooijen, N., MacDonald, A., & Allen, J. (2011) · Science · doi:10.1126/science.1204351 · Cited by 1,427 · see citing works
Guilliams, M., de Kleer, I., Henri, S., Post, S., Vanhoutte, L., Prijck, S. D., Deswarte, K., MALISSEN, B., Hammad, H., & Lambrecht, B. N. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20131199 · Cited by 1,259 · see citing works
Hoeffel, G., Wang, Y., Greter, M., See, P., Teo, P., Malleret, B., Leboeuf, M., Low, D., Oller, G., Almeida, F., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120340 · Cited by 786 · see citing works
Zigmond, E., Varol, C., Farache, J., Elmaliah, E., Satpathy, A. T., Friedlander, G., Mack, M., Shpigel, N. Y., Boneca, I. G., MURPHY, K. M. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.026 · Cited by 754 · see citing works
Self-citationMezzaroma, E., Toldo, S. A., Farkas, D., Seropian, I. M., Tassell, B. W. V., Salloum, F. N., Kannan, H. R., Menna, A. C., Voelkel, N. F., & Abbate, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108586108 · Cited by 631 · see citing works
Satpathy, A. T., Wumesh, K. C., Albring, J. C., Edelson, B. T., Kretzer, N. M., Bhattacharya, D., Murphy, T. L., & MURPHY, K. M. M. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120030 · Cited by 628 · see citing works
Self-citationLiver-resident NK cells confer adaptive immunity in skin-contact inflammation
Peng, H. C., Jiang, X., Chen, Y., Sojka, D. K., Wei, H., Gao, X., Sun, R., Yokoyama, W. M., & Tian, Z. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66381 · Cited by 546 · see citing works
Self-citationvan Amerongen, M. J., Harmsen, M. C., van Rooijen, N., Petersen, A. H., & van Luyn, M. J. A. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060547 · Cited by 544 · see citing works
Leuschner, F., Rauch, P. J., Ueno, T., Gorbatov, R., Marinelli, B. S., Lee, W. W., Dutta, P., Wei, Y., Robbins, C. S., Iwamoto, Y., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111009 · Cited by 519 · see citing works
Mounier, R., Théret, M., Arnold, L., Cuvellier, S., Bultot, L., Göransson, O., Sanz, N., Ferry, A., Sakamoto, K., Foretz, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.017 · Cited by 464 · see citing works
Kumaravelu, P., Hook, L., Morrison, A. M., Ure, J. M., Zhao, S., Zuyev, S., Ansell, J., & Medvinsky, A. (2002) · Development · doi:10.1242/dev.129.21.4891 · Cited by 435 · see citing works
Tsujioka, H., Imanishi, T., Ikejima, H., Kuroi, A., Takarada, S., Tanimoto, T., Kitabata, H., Okochi, K., Arita, Y., Ishibashi, K., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.021 · Cited by 374 · see citing works
Dendritic Cell and Macrophage Heterogeneity In Vivo
Hashimoto, D., Miller, J. C., & Mérad, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.007 · Cited by 366 · see citing works
Davies, L. C., Rosas, M., Jenkins, S. J., Liao, C., Scurr, M. J., Brombacher, F., Fraser, D. J., Allen, J. E., Jones, S. A., & Taylor, P. R. (2013) · Nature Communications · doi:10.1038/ncomms2877 · Cited by 332 · see citing works
Impaired Infarct Healing in Atherosclerotic Mice With Ly-6ChiMonocytosis
Panizzi, P. R., Świrski, F. K., Figueiredo, J., Waterman, P. R., Sosnovik, D. E., Aikawa, E. R., Libby, P., Pittet, M. J., Weissleder, R., & Nahrendorf, M. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.08.089 · Cited by 320 · see citing works
Pinto, A. R., Paolicelli, R., Salimova, E., Gospocic, J., Slonimsky, E., Bilbao-Cortes, D., Godwin, J. W., & Rosenthal, N. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036814 · Cited by 318 · see citing works
Frangogiannis, N. G., Dewald, O., Xia, Y., Ren, G., Haudek, S. B., Leucker, T. M., Kraemer, D., Taffet, G. E., Rollins, B. J., & Entman, M. L. (2007) · Circulation · doi:10.1161/circulationaha.106.646091 · Cited by 289 · see citing works
Tacke, F., Ginhoux, F., Jakubzick, C., van Rooijen, N., Mérad, M., & Randolph, G. J. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052119 · Cited by 282 · see citing works
Self-citationBoyer, S. W., Schroeder, A. V., Smith‐Berdan, S., & Forsberg, E. C. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.04.021 · Cited by 245 · see citing works
Self-citationKaikita, K., Hayasaki, T., Okuma, T., Kuziel, W. A., Ogawa, H., & Takeya, M. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63309-3 · Cited by 206 · see citing works
Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1
Tagliani, E., Shi, C., Nancy, P., Tay, C.-S., Pamer, E. G., & Erlebacher, A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110866 · Cited by 181 · see citing works
GM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions
Zhu, S.-N., Chen, M., Jongstra‐Bilen, J., & Cybulsky, M. I. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090866 · Cited by 166 · see citing works
Origins and functions of phagocytes in the embryo
Lichanska, A. M., & Hume, D. A. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00157-0 · Cited by 150 · see citing works
Søndergaard, C. S., Hess, D. A., Maxwell, D. J., Weinheimer, C. J., Rosová, I., Creer, M. H., Piwnica-Worms, D. R., Kovács, A. D., Pedersen, L., & Nolta, J. A. (2010) · Journal of Translational Medicine · doi:10.1186/1479-5876-8-24 · Cited by 46 · see citing works
Listeriolysin O Is Strongly Immunogenic Independently of Its Cytotoxic Activity
Carrero, J. A., Vivanco-Cid, H., & Unanue, E. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032310 · Cited by 41 · see citing works
Self-citationNeurohormonal control of heart failure
Francis, G. S. (2011) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.78.s1.13 · Cited by 23 · see citing works
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DeNardo, D. G., & Ruffell, B. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0127-6 · Cited by 2,542 · see citing works
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Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., et al. (2015) · Nature · doi:10.1038/nature13989 · Cited by 2,339 · see citing works
The Biological Basis for Cardiac Repair After Myocardial Infarction
Prabhu, S. D., & Frangogiannis, N. G. (2016) · Circulation Research · doi:10.1161/circresaha.116.303577 · Cited by 2,247 · see citing works
From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation
Italiani, P., & Boraschi, D. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00514 · Cited by 2,067 · see citing works
Tissue-Resident Macrophage Ontogeny and Homeostasis
Ginhoux, F., & Guilliams, M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.024 · Cited by 1,884 · see citing works
Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868 · see citing works
Monocytes and macrophages: developmental pathways and tissue homeostasis
Ginhoux, F., & Jung, S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3671 · Cited by 1,840 · see citing works
Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny
Guilliams, M., Ginhoux, F., Jakubzick, C., Naik, S. H., Onai, N., Schraml, B. U., Segura, É., Tussiwand, R., & Yona, S. (2014) · Nature reviews. Immunology · doi:10.1038/nri3712 · Cited by 1,802 · see citing works
Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms
Rőszer, T. (2015) · Mediators of Inflammation · doi:10.1155/2015/816460 · Cited by 1,762 · see citing works
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Epelman, S., Lavine, K. J., & Randolph, G. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.013 · Cited by 1,585 · see citing works
Self-citationFrangogiannis, N. G. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa324 · Cited by 1,229 · see citing works
Origin, fate and dynamics of macrophages at central nervous system interfaces
Goldmann, T., Wieghofer, P., Jordão, M. J. C., Prutek, F., Hagemeyer, N., Frenzel, K., Amann, L., Staszewski, O., Kierdorf, K., Krueger, M., et al. (2016) · Nature Immunology · doi:10.1038/ni.3423 · Cited by 1,209 · see citing works
Self-citationBain, C. C., Bravo-Blas, A., Scott, C. L., Gomez Perdiguero, E., Geissmann, F., Henri, S., Malissen, B., Osborne, L. C., Artis, D., & Mowat, A. M. (2014) · Nature Immunology · doi:10.1038/ni.2967 · Cited by 1,178 · see citing works
Hoeffel, G., Chen, J., Lavin, Y., Low, D., Almeida, F. F., See, P., Beaudin, A. E., Lum, J., Low, I., Forsberg, E. C., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.03.011 · Cited by 1,135 · see citing works
Self-citationChakarov, S., Lim, H. Y., Tan, L., Lim, S. Y., See, P., Lum, J., Zhang, X.-M., Foo, S., Nakamizo, S., Duan, K., et al. (2019) · Science · doi:10.1126/science.aau0964 · Cited by 1,114 · see citing works
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Hulsmans, M., Clauss, S., Xiao, L., Aguirre, A. D., King, K. R., Hanley, A., Hucker, W. J., Wülfers, E. M., Seemann, G., Courties, G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.03.050 · Cited by 1,011 · see citing works
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Macrophages: Development and Tissue Specialization
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The role of macrophages in the resolution of inflammation
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Jakubzick, C. V., Randolph, G. J., & Henson, P. M. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.28 · Cited by 910 · see citing works
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Scott, C. L., Zheng, F., De Baetselier, P., Martens, L., Saeys, Y., De Prijck, S., Lippens, S., Abels, C., Schoonooghe, S., Raes, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms10321 · Cited by 860 · see citing works
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Lavine, K. J., Epelman, S., Uchida, K., Weber, K. J., Nichols, C. G., Schilling, J. D., Ornitz, D. M., Randolph, G. J., & Mann, D. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1406508111 · Cited by 818 · see citing works
Self-citationZhu, Y., Herndon, J. M., Sojka, D. K., Kim, K.-W., Knolhoff, B. L., Zuo, C., Cullinan, D. R., Luo, J. R., Bearden, A. R., Lavine, K. J., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.07.014 · Cited by 799 · see citing works
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Bajpai, G., Bredemeyer, A., Li, W., Zaitsev, K., Koenig, A. L., Lokshina, I., Mohan, J., Ivey, B., Hsiao, H.-M., Weinheimer, C., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314028 · Cited by 751 · see citing works
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Cardiac monocytes and macrophages after myocardial infarction
Peet, C. J., Ívetic, A., Bromage, D. I., & Shah, A. M. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz336 · Cited by 608 · see citing works
Heidt, T., Courties, G., Dutta, P., Sager, H. B., Sebas, M., Iwamoto, Y., Sun, Y., Da Silva, N., Panizzi, P., van der Laan, A. M., et al. (2014) · Circulation Research · doi:10.1161/circresaha.115.303567 · Cited by 607 · see citing works
Schneider, C., Nobs, S. P., Kurrer, M. O., Rehrauer, H., Thiele, C., & Köpf, M. (2014) · Nature Immunology · doi:10.1038/ni.3005 · Cited by 603 · see citing works
Tissue macrophages: heterogeneity and functions
Gordon, S., & Plüddemann, A. (2017) · BMC Biology · doi:10.1186/s12915-017-0392-4 · Cited by 601 · see citing works
Haenseler, W., Sansom, S. N., Buchrieser, J., Newey, S. E., Moore, C. S., Nicholls, F. J., Chintawar, S., Schnell, C., Antel, J. P., Allen, N. D., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.017 · Cited by 593 · see citing works
Preparing the ground for tissue regeneration: from mechanism to therapy
Forbes, S. J., & Rosenthal, N. A. (2014) · Nature Medicine · doi:10.1038/nm.3653 · Cited by 585 · see citing works
Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation
Prinz, M., Masuda, T., Wheeler, M. A., & Quintana, F. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-110159 · Cited by 584 · see citing works
IRF3 and type I interferons fuel a fatal response to myocardial infarction
King, K. R., Aguirre, A. D., Ye, Y., Sun, Y., Roh, J. D., Ng, R. P., Köhler, R. H., Arlauckas, S. P., Iwamoto, Y., Savol, A. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4428 · Cited by 571 · see citing works
Skelly, D. A., Squiers, G. T., McLellan, M. A., Bolisetty, M. T., Robson, P., Rosenthal, N. A., & Pinto, A. R. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.072 · Cited by 551 · see citing works
Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny
Huang, L., Nazarova, E. V., Tan, S., Liu, Y., & Russell, D. G. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20172020 · Cited by 550 · see citing works
Obesity, Hypertension, and Cardiac Dysfunction
Mouton, A. J., Li, X., Hall, M. E., & Hall, J. E. (2020) · Circulation Research · doi:10.1161/circresaha.119.312321 · Cited by 549 · see citing works
An acute immune response underlies the benefit of cardiac stem cell therapy
Vagnozzi, R. J., Maillet, M., Sargent, M. A., Khalil, H., Johansen, A. K. Z., Schwanekamp, J. A., York, A. J., Huang, V. H., Nahrendorf, M., Sadayappan, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1802-2 · Cited by 547 · see citing works
Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing
Boniakowski, A. E., Kimball, A., Jacobs, B. N., Kunkel, S. L., & Gallagher, K. A. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700223 · Cited by 546 · see citing works
Farbehi, N., Patrick, R., Dorison, A., Xaymardan, M., Janbandhu, V. C., Wystub-Lis, K., Ho, J. W. K., Nordon, R. E., & Harvey, R. P. (2019) · eLife · doi:10.7554/elife.43882 · Cited by 546 · see citing works
Dick, S. A., Wong, A., Hamidzada, H., Nejat, S., Nechanitzky, R., Vohra, S., Mueller, B., Zaman, R., Kantores, C., Aronoff, L., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abf7777 · Cited by 538 · see citing works
Self-citationBain, C. C., Hawley, C. A., Garner, H., Scott, C. L., Schridde, A., Steers, N. J., Mack, M., Joshi, A., Guilliams, M., Mowat, A. M. I., et al. (2016) · Nature Communications · doi:10.1038/ncomms11852 · Cited by 527 · see citing works
Abandoning M1/M2 for a Network Model of Macrophage Function
Nahrendorf, M., & Swirski, F. K. (2016) · Circulation Research · doi:10.1161/circresaha.116.309194 · Cited by 525 · see citing works
Mack, M. (2017) · Matrix Biology · doi:10.1016/j.matbio.2017.11.010 · Cited by 516 · see citing works
TAM Receptor Signaling in Immune Homeostasis
Rothlin, C. V., Silva, E. A. C., Bosurgi, L., & Ghosh, S. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112103 · Cited by 516 · see citing works
Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?
Parisi, L., Gini, E., Baci, D., Tremolati, M., Fanuli, M., Bassani, B., Farronato, G., Bruno, A., & Mortara, L. (2018) · Journal of Immunology Research · doi:10.1155/2018/8917804 · Cited by 508 · see citing works
Progressive replacement of embryo-derived cardiac macrophages with age
Molawi, K., Wolf, Y., Kandalla, P. K., Favret, J., Hagemeyer, N., Frenzel, K., Pinto, A. R., Klapproth, K., Henri, S., MALISSEN, B., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20140639 · Cited by 504 · see citing works
Cardiac macrophages promote diastolic dysfunction
Hulsmans, M., Sager, H. B., Roh, J. D., Valero‐Muñoz, M., Houstis, N. E., Iwamoto, Y., Sun, Y., Wilson, R. M., Wojtkiewicz, G. R., Tricot, B., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171274 · Cited by 498 · see citing works
Monocyte Conversion During Inflammation and Injury.
Kratofil, R. M., Kubes, P., & Deniset, J. (2017) · Arteriosclerosis, Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.308198 · Cited by 386 · see citing works
The origins and functions of dendritic cells and macrophages in the skin
MALISSEN, B., Tamoutounour, S., & Henri, S. (2014) · Nature reviews. Immunology · doi:10.1038/nri3683 · Cited by 484 · see citing works
Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure
Koenig, A. L., Shchukina, I., Amrute, J., Andhey, P. S., Zaitsev, K., Lai, L., Bajpai, G., Bredemeyer, A., Smith, G., Jones, C., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00028-6 · Cited by 482 · see citing works
Self-citationMost Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells
Sheng, J., Ruedl, C., & Karjalainen, K. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.016 · Cited by 482 · see citing works
Russo, I., & Frangogiannis, N. G. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.12.011 · Cited by 481 · see citing works
Zigmond, E., Samia-Grinberg, S., Pasmanik‐Chor, M., Brazowski, E., Shibolet, O., Halpern, Z., & Varol, C. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400574 · Cited by 477 · see citing works
Three Unique Interstitial Macrophages in the Murine Lung at Steady State
Gibbings, S. L., Thomas, S. M., Atif, S. M., McCubbrey, A. L., Desch, A. N., Danhorn, T., Leach, S. M., Bratton, D. L., Henson, P. M., Janssen, W. J., et al. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0361oc · Cited by 476 · see citing works
Blériot, C., Dupuis, T., Jouvion, G., Eberl, G., Disson, O., & Lecuit, M. (2015) · Immunity · doi:10.1016/j.immuni.2014.12.020 · Cited by 471 · see citing works
Adipose tissue macrophages: going off track during obesity
Boutens, L., & Stienstra, R. (2016) · Diabetologia · doi:10.1007/s00125-016-3904-9 · Cited by 430 · see citing works
Monocytes and macrophages in abdominal aortic aneurysm
Raffort, J., Lareyre, F., Clément, M., Hassen‐Khodja, R., Chinetti, G., & Mallat, Z. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.52 · Cited by 426 · see citing works
Sano, S., Oshima, K., Wang, Y., Katanasaka, Y., Sano, M., & Walsh, K. (2018) · Circulation Research · doi:10.1161/circresaha.118.313225 · Cited by 417 · see citing works
Macrophages at CNS interfaces: Ontogeny and function in health and disease
Kierdorf, K., Masuda, T., Jordão, M. J. C., & Prinz, M. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0201-x · Cited by 416 · see citing works
Cronk, J. C., Filiano, A. J., Louveau, A., Marin, I., Marsh, R., Ji, E., Goldman, D. H., Smirnov, I., Geraci, N., Acton, S., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180247 · Cited by 412 · see citing works
Proliferation and recruitment contribute to myocardial macrophage expansion in chronic heart failure
Sager, H., Hulsmans, M., Lavine, K. J., Moreira, M. B., Heidt, T., Courties, G., Sun, Y., Iwamoto, Y., Tricot, B., Khan, O. F., et al. (2016) · Circulation Research · doi:10.1161/circresaha.116.309001 · Cited by 377 · see citing works
Self-citationDoes niche competition determine the origin of tissue-resident macrophages?
Guilliams, M., & Scott, C. L. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.42 · Cited by 409 · see citing works
Ma, Y., Mouton, A. J., & Lindsey, M. L. (2018) · Translational Research · doi:10.1016/j.trsl.2017.10.001 · Cited by 405 · see citing works
Role of Cardiac Macrophages on Cardiac Inflammation, Fibrosis and Tissue Repair
Lafuse, W. P., Wozniak, D. J., & Rajaram, M. V. S. (2020) · Cells · doi:10.3390/cells10010051 · Cited by 400 · see citing works
Fetal monocytes and the origins of tissue-resident macrophages
Hoeffel, G., & Ginhoux, F. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.01.001 · Cited by 393 · see citing works
Lim, H. Y., Lim, S. Y., Tan, C. K., Thiam, C. H., Goh, C. C., Carbajo, D., Chew, S. H. S., See, P., Chakarov, S., Wang, X. N., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.06.008 · Cited by 384 · see citing works
Inflammation and fibrosis in murine models of heart failure
Bacmeister, L., Schwarzl, M., Warnke, S., Stoffers, B., Blankenberg, S., Westermann, D., & Lindner, D. (2019) · Basic Research in Cardiology · doi:10.1007/s00395-019-0722-5 · Cited by 384 · see citing works
Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets
Chen, R., Zhang, H., Tang, B., Luo, Y., Yang, Y., Zhong, X., Chen, S., Xu, X., Huang, S., & Liu, C. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01840-1 · Cited by 387 · see citing works
Daemen, S., Gainullina, A., Kalugotla, G., He, L., Chan, M. M., Beals, J. W., Liss, K. H., Klein, S., Feldstein, A. E., Finck, B. N., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108626 · Cited by 378 · see citing works
“Cx3cr1-GFP, CD115-CreER; R26tdTomato (C57BL6/J background) were obtained from Dr. Gwendolyn Randolph.”
InfluentialSelf-citationMonocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design
Ogle, M. E., Segar, C. E., Sridhar, S., & Botchwey, E. A. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216650293 · Cited by 378 · see citing works
Ensan, S., Li, A., Besla, R., Degousee, N., Cosme, J., Roufaiel, M., Shikatani, E. A., El-Maklizi, M., Williams, J. W., Robins, L., et al. (2016) · Nature Immunology · doi:10.1038/ni.3343 · Cited by 372 · see citing works
Self-citationTissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Guan, F., Wang, R., Yi, Z., Luo, P., Liu, W., Xie, Y., Liu, Z., Xia, Z., Zhang, H., & Cheng, Q. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02124-y · Cited by 371 · see citing works
Ontogeny of Tissue-Resident Macrophages
Hoeffel, G., & Ginhoux, F. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00486 · Cited by 364 · see citing works
Navegantes, K. C., Gomes, R. D. S., Pereira, P. A., Czaikoski, P. G., Azevedo, C., & Monteiro, M. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1141-8 · Cited by 340 · see citing works
Stress and Inflammation in Coronary Artery Disease: A Review Psychoneuroendocrineimmunology-Based
Fioranelli, M., Bottaccioli, A. G., Bottaccioli, F., Bianchi, M., Rovesti, M., & Roccia, M. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02031 · Cited by 358 · see citing works
Origin, Differentiation, and Function of Intestinal Macrophages
Bain, C. C., & Schridde, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02733 · Cited by 348 · see citing works
Alternatively activated macrophages determine repair of the infarcted adult murine heart
Shiraishi, M., Shintani, Y., Shintani, Y., Ishida, H., Saba, R., Yamaguchi, A., Adachi, H., Yashiro, K., & Suzuki, K. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85782 · Cited by 344 · see citing works
Martini, E., Kunderfranco, P., Peano, C., Carullo, P., Cremonesi, M., Schorn, T., Carriero, R., Termanini, A., Colombo, F. S., Jachetti, E., et al. (2019) · Circulation · doi:10.1161/circulationaha.119.041694 · Cited by 341 · see citing works
Tissue‐resident macrophages: then and now
Davies, L. C., & Taylor, P. R. (2015) · Immunology · doi:10.1111/imm.12451 · Cited by 333 · see citing works
Immune Cell and Other Noncardiomyocyte Regulation of Cardiac Hypertrophy and Remodeling
Frieler, R. A., & Mortensen, R. M. (2015) · Circulation · doi:10.1161/circulationaha.114.008788 · Cited by 330 · see citing works
Primitive Embryonic Macrophages are Required for Coronary Development and Maturation
Leid, J. M., Carrelha, J., Boukarabila, H., Epelman, S., Jacobsen, S. E. W., & Lavine, K. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.308270 · Cited by 327 · see citing works
Self-citation
- Authors
- Epelman, S., Lavine, K. J., Beaudin, A. E., Sojka, D. K., Carrero, J. A., Calderon, B., Brija, T., Gautier, E. L., Ivanov, S., Satpathy, A. T., Schilling, J. D., Schwendener, R., Sergin, I., Razani, B., Forsberg, E. C., Yokoyama, W. M., Unanue, E. R., Colonna, M., Randolph, G. J., & Mann, D. L.
- Affiliations
- Washington University in St. Louis (US)
- University of California, Santa Cruz (US)
- University of Zurich (CH)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Mann, Douglas L.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 40
- Issue
- 1
- Pages
- 91-104
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3923301
- OpenAlex
- W2010484682
- Cited by
- 1,494
- References
- 34
- Citations by year
- 2026: 101 · 2025: 113 · 2024: 131 · 2023: 135 · 2022: 140 · 2021: 147 · 2020: 147 · 2019: 117 · 2018: 128 · 2017: 117 · 2016: 80 · 2015: 77 · 2014: 59
- FWCI
- 76.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- HAL (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (K08HL112826, R01HL111094, T32HL007081)
- National Cancer Institute (T32CA009547)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100917)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- cardiac macrophages, tissue-resident macrophages, monocyte-derived macrophages, embryonic macrophages, yolk sac macrophages, monocyte proliferation, Ly6C+ monocytes, CCR2, cardiac inflammation, efferocytosis, antigen sampling, macrophage homeostasis
- MeSH terms
- Animals, Antigens, Ly, Cell Differentiation, Cells, Cultured, Heart, Homeostasis, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Myocarditis, Myocardium, Phagocytosis, Yolk Sac, Cell Death, Antigen Presentation, Cell Lineage, Myocytes, Cardiac, Fetal Development, Mice, Receptors, CCR2, Transcriptome
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