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New Insights Into Tissue Macrophages: From Their Origin to the Development of Memory

  • Italiani, Paola (Institute of Protein Biochemistry, National Research Council) ;
  • Boraschi, Diana (Institute of Protein Biochemistry, National Research Council)
  • Received : 2015.05.30
  • Accepted : 2015.08.04
  • Published : 2015.08.31
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Abstract

Macrophages are the main effector cells of innate immunity and are involved in inflammatory and anti-infective processes. They also have an essential role in maintaining tissue homeostasis, supporting tissue development, and repairing tissue damage. Until few years ago, it was believed that tissue macrophages derived from circulating blood monocytes, which terminally differentiated in the tissue and unable to proliferate. Recent evidence in the biology of tissue macrophages has uncovered a series of immune and ontogenic features that had been neglected for long, despite old observations. These include origin, heterogeneity, proliferative potential (or self-renewal), polarization, and memory. In recent years, the number of publications on tissue resident macrophages has grown rapidly, highlighting the renewed interest of the immunologists for these key players of innate immunity. This minireview aims to summarizing the new current knowledge in macrophage immunobiology, in order to offer a clear and immediate overview of the field.

Keywords

References

  1. Buchmann, K. 2014. Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals. Front. Immunol. 5: 459.
  2. Wong, B. W., A. Meredith, D. Lin, and B. M. McManus. 2012. The biological role of inflammation in atherosclerosis. Can. J. Cardiol. 28: 631-641. https://doi.org/10.1016/j.cjca.2012.06.023
  3. Viola, J., and O. Soehnlein. 2015. Atherosclerosis - A matter of unresolved inflammation. Semin. Immunol. 27: 184-193. https://doi.org/10.1016/j.smim.2015.03.013
  4. Mantovani, A., P. Allavena, A. Sica, and F. Balkwill. 2008. Cancer-related inflammation. Nature 454: 436-444. https://doi.org/10.1038/nature07205
  5. Simon, A., and J. W. van der Meer. 2007. Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R86-R98. https://doi.org/10.1152/ajpregu.00504.2006
  6. Masters, S. L., A. Simon, I. Aksentijevich, and D. L. Kastner. 2009. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu. Rev. Immunol. 27: 621-668. https://doi.org/10.1146/annurev.immunol.25.022106.141627
  7. Dinarello, C. A., and J. W. van der Meer. 2013. Treating inflammation by blocking interleukin-1 in humans. Semin. Immunol. 25: 469-484. https://doi.org/10.1016/j.smim.2013.10.008
  8. Cavaillon, J. M. 2011. The historical milestones in the understanding of leukocyte biology initiated by Elie Metchnikoff. J. Leukoc. Biol. 90: 413-424. https://doi.org/10.1189/jlb.0211094
  9. Aschoff, J. 1924. Das reticuloendothelial system. Erg. Inn. Med. Kinderheilk. 26: 1-119.
  10. van, F. R., and Z. A. Cohn. 1968. The origin and kinetics of mononuclear phagocytes. J. Exp. Med. 128: 415-435. https://doi.org/10.1084/jem.128.3.415
  11. van, F. R., and M. M. esselhoff-den Dulk. 1984. Dual origin of mouse spleen macrophages. J. Exp. Med. 160: 1273-1283. https://doi.org/10.1084/jem.160.5.1273
  12. Parwaresch, M. R., and H. H. Wacker. 1984. Origin and kinetics of resident tissue macrophages. Parabiosis studies with radiolabelled leucocytes. Cell Tissue Kinet. 17: 25-39.
  13. Czernielewski, J. M., and M. Demarchez. 1987. Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J. Invest. Dermatol. 88: 17-20. https://doi.org/10.1111/1523-1747.ep12464659
  14. Melnicoff, M. J., P. K. Horan, E. W. Breslin, and P. S. Morahan. 1988. Maintenance of peritoneal macrophages in the steady state. J. Leukoc. Biol. 44: 367-375. https://doi.org/10.1002/jlb.44.5.367
  15. Schulz, C., P. E. Gomez, L. Chorro, H. Szabo-Rogers, N. Cagnard, K. Kierdorf, M. Prinz, B. Wu, S. E. Jacobsen, J. W. Pollard, J. Frampton, K. J. Liu, and F. Geissmann. 2012. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336: 86-90. https://doi.org/10.1126/science.1219179
  16. Gentek, R., K. Molawi, and M. H. Sieweke. 2014. Tissue macrophage identity and self-renewal. Immunol. Rev. 262: 56-73. https://doi.org/10.1111/imr.12224
  17. Ley, K., Y. I. Miller, and C. C. Hedrick. 2011. Monocyte and macrophage dynamics during atherogenesis. Arterioscler. Thromb. Vasc. Biol. 31: 1506-1516. https://doi.org/10.1161/ATVBAHA.110.221127
  18. Italiani, P., and D. Boraschi. 2014. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front. Immunol. 5: 514.
  19. Epelman, S., K. J. Lavine, and G. J. Randolph. 2014. Origin and functions of tissue macrophages. Immunity 41: 21-35. https://doi.org/10.1016/j.immuni.2014.06.013
  20. Haldar, M., and K. M. Murphy. 2014. Origin, development, and homeostasis of tissue-resident macrophages. Immunol. Rev. 262: 25-35. https://doi.org/10.1111/imr.12215
  21. Yona, S., K. W. Kim, Y. Wolf, A. Mildner, D. Varol, M. Breker, D. Strauss-Ayali, S. Viukov, M. Guilliams, A. Misharin, D. A. Hume, H. Perlman, B. Malissen, E. Zelzer, and S. Jung. 2013. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38: 79-91. https://doi.org/10.1016/j.immuni.2012.12.001
  22. Gomez, P. E., and F. Geissmann. 2013. Myb-independent macrophages: a family of cells that develops with their tissue of residence and is involved in its homeostasis. Cold Spring Harb. Symp. Quant. Biol. 78: 91-100. https://doi.org/10.1101/sqb.2013.78.020032
  23. Cumano, A., and I. Godin. 2007. Ontogeny of the hematopoietic system. Annu. Rev. Immunol. 25: 745-785. https://doi.org/10.1146/annurev.immunol.25.022106.141538
  24. Gomez, P. E., K. Klapproth, C. Schulz, K. Busch, E. Azzoni, L. Crozet, H. Garner, C. Trouillet, M. F. de Bruijn, F. Geissmann, and H. R. Rodewald. 2015. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 518: 547-551. https://doi.org/10.1038/nature13989
  25. Tamoutounour, S., M. Guilliams, S. F. Montanana, H. Liu, D. Terhorst, C. Malosse, E. Pollet, L. Ardouin, H. Luche, C. Sanchez, M. Dalod, B. Malissen, and S. Henri. 2013. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39: 925-938. https://doi.org/10.1016/j.immuni.2013.10.004
  26. Zigmond, E., and S. Jung. 2013. Intestinal macrophages: well educated exceptions from the rule. Trends Immunol. 34: 162-168. https://doi.org/10.1016/j.it.2013.02.001
  27. Bain, C. C., A. Bravo-Blas, C. L. Scott, P. E. Gomez, F. Geissmann, S. Henri, B. Malissen, L. C. Osborne, D. Artis, and A. M. Mowat. 2014. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15: 929-937. https://doi.org/10.1038/ni.2967
  28. Davies, L. C., M. Rosas, S. J. Jenkins, C. T. Liao, M. J. Scurr, F. Brombacher, D. J. Fraser, J. E. Allen, S. A. Jones, and P. R. Taylor. 2013. Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation. Nat. Commun. 4: 1886. https://doi.org/10.1038/ncomms2877
  29. Molawi, K., Y. Wolf, P. K. Kandalla, J. Favret, N. Hagemeyer, K. Frenzel, A. R. Pinto, K. Klapproth, S. Henri, B. Malissen, H. R. Rodewald, N. A. Rosenthal, M. Bajenoff, M. Prinz, S. Jung, and M. H. Sieweke. 2014. Progressive replacement of embryo-derived cardiac macrophages with age. J. Exp. Med. 211: 2151-2158. https://doi.org/10.1084/jem.20140639
  30. Varol, C., A. Mildner, and S. Jung. 2015. Macrophages: development and tissue specialization. Annu. Rev. Immunol. 33: 643-675. https://doi.org/10.1146/annurev-immunol-032414-112220
  31. Dey, A., J. Allen, and P. A. Hankey-Giblin. 2014. Ontogeny and polarization of macrophages in inflammation: blood monocytes versus tissue macrophages. Front. Immunol. 5: 683.
  32. Mills, C. D. 2012. M1 and M2 Macrophages: Oracles of Health and Disease. Crit. Rev. Immunol. 32: 463-488. https://doi.org/10.1615/CritRevImmunol.v32.i6.10
  33. Gordon, S., and P. R. Taylor. 2005. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5: 953-964. https://doi.org/10.1038/nri1733
  34. Gordon, S. 2003. Alternative activation of macrophages. Nat. Rev. Immunol. 3: 23-35. https://doi.org/10.1038/nri978
  35. Martinez, F. O., A. Sica, A. Mantovani, and M. Locati. 2008. Macrophage activation and polarization. Front. Biosci. 13: 453-461. https://doi.org/10.2741/2692
  36. Sica, A., and A. Mantovani. 2012. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122: 787-795. https://doi.org/10.1172/JCI59643
  37. Murray, P. J., and T. A. Wynn. 2011. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11: 723-737. https://doi.org/10.1038/nri3073
  38. Mantovani, A., A. Sica, S. Sozzani, P. Allavena, A. Vecchi, and M. Locati. 2004. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25: 677-686. https://doi.org/10.1016/j.it.2004.09.015
  39. Galvan-Pena, S., and L. A. O'Neill. 2014. Metabolic reprograming in macrophage polarization. Front. Immunol. 5: 420.
  40. Rath, M., I. Muller, P. Kropf, E. I. Closs, and M. Munder. 2014. Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Front. Immunol. 5: 532.
  41. Mosser, D. M., and J. P. Edwards. 2008. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8: 958-969. https://doi.org/10.1038/nri2448
  42. Martinez, F. O., and S. Gordon. 2014. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime. Rep. 6: 13.
  43. Murray, P. J., J. E. Allen, S. K. Biswas, E. A. Fisher, D. W. Gilroy, S. Goerdt, S. Gordon, J. A. Hamilton, L. B. Ivashkiv, T. Lawrence, M. Locati, A. Mantovani, F. O. Martinez, J. L. Mege, D. M. Mosser, G. Natoli, J. P. Saeij, J. L. Schultze, K. A. Shirey, A. Sica, J. Suttles, I. Udalova, J. A. van Ginderachter, S. N. Vogel, and T. A. Wynn. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41: 14-20. https://doi.org/10.1016/j.immuni.2014.06.008
  44. Xue, J., S. V. Schmidt, J. Sander, A. Draffehn, W. Krebs, I. Quester, N. D. De, T. D. Gohel, M. Emde, L. Schmidleithner, H. Ganesan, A. Nino-Castro, M. R. Mallmann, L. Labzin, H. Theis, M. Kraut, M. Beyer, E. Latz, T. C. Freeman, T. Ulas, and J. L. Schultze. 2014. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40: 274-288. https://doi.org/10.1016/j.immuni.2014.01.006
  45. Butovsky, O., M. P. Jedrychowski, C. S. Moore, R. Cialic, A. J. Lanser, G. Gabriely, T. Koeglsperger, B. Dake, P. M. Wu, C. E. Doykan, Z. Fanek, L. Liu, Z. Chen, J. D. Rothstein, R. M. Ransohoff, S. P. Gygi, J. P. Antel, and H. L. Weiner. 2014. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17: 131-143. https://doi.org/10.1038/nn.3599
  46. Okabe, Y., and R. Medzhitov. 2014. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157: 832-844. https://doi.org/10.1016/j.cell.2014.04.016
  47. Italiani, P., E. M. Mazza, D. Lucchesi, I. Cifola, C. Gemelli, A. Grande, C. Battaglia, S. Bicciato, and D. Boraschi. 2014. Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro. PLoS One 9: e87680. https://doi.org/10.1371/journal.pone.0087680
  48. Kraakman, M. J., A. J. Murphy, K. Jandeleit-Dahm, and H. L. Kammoun. 2014. Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function? Front. Immunol. 5: 470.
  49. Biswas, S. K., and A. Mantovani. 2010. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11: 889-896. https://doi.org/10.1038/ni.1937
  50. Soumelis, V., L. Pattarini, P. Michea, and A. Cappuccio. 2015. Systems approaches to unravel innate immune cell diversity, environmental plasticity and functional specialization. Curr. Opin. Immunol. 32: 42-47. https://doi.org/10.1016/j.coi.2014.12.007
  51. Ziegler-Heitbrock, L., and T. P. Hofer. 2013. Toward a refined definition of monocyte subsets. Front. Immunol. 4: 23.
  52. Molawi, K., and M. H. Sieweke. 2013. Transcriptional control of macrophage identity, self-renewal, and function. Adv. Immunol. 120: 269-300. https://doi.org/10.1016/B978-0-12-417028-5.00010-7
  53. Gautier, E. L., and L. Yvan-Charvet. 2014. Understanding macrophage diversity at the ontogenic and transcriptomic levels. Immunol. Rev. 262: 85-95. https://doi.org/10.1111/imr.12231
  54. Kohyama, M., W. Ise, B. T. Edelson, P. R. Wilker, K. Hildner, C. Mejia, W. A. Frazier, T. L. Murphy, and K. M. Murphy. 2009. Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457: 318-321. https://doi.org/10.1038/nature07472
  55. Gonzalez, N., J. A. Guillen, G. Gallardo, M. Diaz, J. V. de la Rosa, I. H. Hernandez, M. Casanova-Acebes, F. Lopez, C. Tabraue, S. Beceiro, C. Hong, P. C. Lara, M. Andujar, S. Arai, T. Miyazaki, S. Li, A. L. Corbi, P. Tontonoz, A. Hidalgo, and A. Castrillo. 2013. The nuclear receptor LXRalpha controls the functional specialization of splenic macrophages. Nat. Immunol. 14: 831-839. https://doi.org/10.1038/ni.2622
  56. Schneider, C., S. P. Nobs, M. Kurrer, H. Rehrauer, C. Thiele, and M. Kopf. 2014. Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat. Immunol. 15: 1026-1037. https://doi.org/10.1038/ni.3005
  57. Lawrence, T., and G. Natoli. 2011. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat. Rev. Immunol. 11: 750-761. https://doi.org/10.1038/nri3088
  58. Gosselin, D., V. M. Link, C. E. Romanoski, G. J. Fonseca, D. Z. Eichenfield, N. J. Spann, J. D. Stender, H. B. Chun, H. Garner, F. Geissmann, and C. K. Glass. 2014. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159: 1327-1340. https://doi.org/10.1016/j.cell.2014.11.023
  59. Lavin, Y., D. Winter, R. Blecher-Gonen, E. David, H. Keren-Shaul, M. Merad, S. Jung, and I. Amit. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159: 1312-1326. https://doi.org/10.1016/j.cell.2014.11.018
  60. Zigmond, E., B. Bernshtein, G. Friedlander, C. R. Walker, S. Yona, K. W. Kim, O. Brenner, R. Krauthgamer, C. Varol, W. Muller, and S. Jung. 2014. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40: 720-733. https://doi.org/10.1016/j.immuni.2014.03.012
  61. Butovsky, O., M. P. Jedrychowski, C. S. Moore, R. Cialic, A. J. Lanser, G. Gabriely, T. Koeglsperger, B. Dake, P. M. Wu, C. E. Doykan, Z. Fanek, L. Liu, Z. Chen, J. D. Rothstein, R. M. Ransohoff, S. P. Gygi, J. P. Antel, and H. L. Weiner. 2014. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17: 131-143. https://doi.org/10.1038/nn.3599
  62. Perry, V. H., and J. Teeling. 2013. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Semin. Immunopathol. 35: 601-612. https://doi.org/10.1007/s00281-013-0382-8
  63. Wolf, Y., S. Yona, K. W. Kim, and S. Jung. 2013. Microglia, seen from the CX3CR1 angle. Front. Cell. Neurosci. 7: 26.
  64. Boyle, W. J., W. S. Simonet, and D. L. Lacey. 2003. Osteoclast differentiation and activation. Nature 423: 337-342. https://doi.org/10.1038/nature01658
  65. Guilliams, M., F. Ginhoux, C. Jakubzick, S. H. Naik, N. Onai, B. U. Schraml, E. Segura, R. Tussiwand, and S. Yona. 2014. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat. Rev. Immunol. 14: 571-578. https://doi.org/10.1038/nri3712
  66. Boraschi, D., and M. S. Meltzer. 1979. Defective tumoricidal capacity of macrophages from A/J mice. II. Comparison of the macrophage cytotoxic defect of A/J mice with that of lipid A-unresponsive C3H/HeJ mice. J. Immunol. 122: 1592-1597.
  67. Tagliabue, A., D. Boraschi, and J. L. McCoy. 1980. Development of cell-mediated antiviral immunity and macrophage activation in C3H/HeN mice infected with mouse mammary tumor virus. J. Immunol. 124: 2203-2208.
  68. Netea, M. G., J. Quintin, and J. W. van der Meer. 2011. Trained immunity: a memory for innate host defense. Cell Host Microbe 9: 355-361. https://doi.org/10.1016/j.chom.2011.04.006
  69. Durrant, W. E., and X. Dong. 2004. Systemic acquired resistance. Annu. Rev. Phytopathol. 42: 185-209. https://doi.org/10.1146/annurev.phyto.42.040803.140421
  70. Bowdish, D. M., M. S. Loffredo, S. Mukhopadhyay, A. Mantovani, and S. Gordon. 2007. Macrophage receptors implicated in the "adaptive" form of innate immunity. Microbes. Infect. 9: 1680-1687. https://doi.org/10.1016/j.micinf.2007.09.002
  71. Quintin, J., S. Saeed, J. H. Martens, E. J. Giamarellos-Bourboulis, D. C. Ifrim, C. Logie, L. Jacobs, T. Jansen, B. J. Kullberg, C. Wijmenga, L. A. Joosten, R. J. Xavier, J. W. van der Meer, H. G. Stunnenberg, and M. G. Netea. 2012. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12: 223-232. https://doi.org/10.1016/j.chom.2012.06.006
  72. Saeed, S., J. Quintin, H. H. Kerstens, N. A. Rao, A. Aghajanirefah, F. Matarese, S. C. Cheng, J. Ratter, K. Berentsen, M. A. van der Ent, N. Sharifi, E. M. Janssen-Megens, H. M. Ter, A. Mandoli, S. T. van, A. Ng, F. Burden, K. Downes, M. Frontini, V. Kumar, E. J. Giamarellos-Bourboulis, W. H. Ouwehand, J. W. van der Meer, L. A. Joosten, C. Wijmenga, J. H. Martens, R. J. Xavier, C. Logie, M. G. Netea, and H. G. Stunnenberg. 2014. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345: 1251086. https://doi.org/10.1126/science.1251086
  73. Foster, S. L., D. C. Hargreaves, and R. Medzhitov. 2007. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447: 972-978. https://doi.org/10.1038/nature05836
  74. Biswas, S. K., and A. Mantovani. 2012. Orchestration of metabolism by macrophages. Cell Metab. 15: 432-437. https://doi.org/10.1016/j.cmet.2011.11.013
  75. Martinez, F. O., and S. Gordon. 2015. The evolution of our understanding of macrophages and translation of findings toward the clinic. Expert Rev. Clin. Immunol. 11: 5-13.
  76. Jaitin, D. A., E. Kenigsberg, H. Keren-Shaul, N. Elefant, F. Paul, I. Zaretsky, A. Mildner, N. Cohen, S. Jung, A. Tanay, and I. Amit. 2014. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343: 776-779. https://doi.org/10.1126/science.1247651

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