In this issue of the Journal of Innate Immunity, we are privileged to publish an article by Siamon Gordon [1], Professor Emeritus of Cellular Pathology at the University of Oxford, commemorating the life and achievements of Elie Metchnikoff (1845-1916). Siamon Gordon is an outstanding scientist in the field of macrophage research and has made many important discoveries, e.g. the pattern recognition receptor dectin-1 [2].
Elie Metchnikoff and Paul Ehrlich shared the Nobel Prize in Physiology or Medicine in 1908 and both may be considered the founders of innate immunity, even if Charles Janeway was the one who conceptualized this entity of host defense many years later. The groundbreaking discovery of phagocytosis in 1882 and the personal life of Elie Metchnikoff continue to fascinate [3].
From an earlier rather simplistic view of macrophages, this area has expanded rapidly in recent years, to now include a large number of complex phenotypes [4]. In addition, important roles in a broad range of disease conditions, such as atherosclerosis, sepsis, bacterial infection, allergic inflammation, autophagy and viral infections, have been established [5, 6, 7, 8, 9, 10, 11, 12, 13]. Further emphasizing their importance, macrophages and cells with macrophage-like properties occurred early during evolution [14, 15].
In a research context that is becoming increasingly complex, a holistic view on macrophages is helpful. A very interesting review on M1 and M2 macrophages by Charles D. Mills and Klaus Ley [16] was recently published in this journal. ‘Inhibit’ type macrophages (called M1) can rapidly kill pathogens, and are thus part of the primary host defense while ‘Heal’ type macrophages (M2) routinely repair and maintain tissue integrity. The increasing number of observed anomalies that accumulate can be the origin of new paradigms.
Heiko Herwald, Lund
Arne Egesten, Lund
References
- 1.Gordon S. Elie Metchnikoff, the man and the myth. J Innate Immun. 2016;8:223–227. doi: 10.1159/000443331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Brown GD, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature. 2001;413:36–37. doi: 10.1038/35092620. [DOI] [PubMed] [Google Scholar]
- 3.Gordon S. Phagocytosis: an immunobiologic process. Immunity. 2016;44:463–475. doi: 10.1016/j.immuni.2016.02.026. [DOI] [PubMed] [Google Scholar]
- 4.Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science. 2010;327:656–661. doi: 10.1126/science.1178331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013;13:709–721. doi: 10.1038/nri3520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Koziel J, Chmiest D, Bryzek D, Kmiecik K, Mizgalska D, Maciag-Gudowska A, Shaw LN, Potempa J. The Janus face of α-toxin: a potent mediator of cytoprotection in staphylococci-infected macrophages. J Innate Immun. 2015;7:187–198. doi: 10.1159/000368048. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.McClure C, Brudecki L, Yao ZQ, McCall CE, El Gazzar., M Processing body formation limits proinflammatory cytokine synthesis in endotoxin-tolerant monocytes and murine septic macrophages. J Innate Immun. 2015;7:572–583. doi: 10.1159/000381915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Sheikh F, Dickensheets H, Pedras-Vasconcelos J, Ramalingam T, Helming L, Gordon S, Donnelly RP. The interleukin-13 receptor-α1 chain is essential for induction of the alternative macrophage activation pathway by IL-13 but not IL-4. J Innate Immun. 2015;7:494–505. doi: 10.1159/000376579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Stranks AJ, Hansen AL, Panse I, Mortensen M, Ferguson DJ, Puleston DJ, Shenderov K, Watson AS, Veldhoen M, Phadwal K, Cerundolo V, Simon AK. Autophagy controls acquisition of aging features in macrophages. J Innate Immun. 2015;7:375–391. doi: 10.1159/000370112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Terry RL, Deffrasnes C, Getts DR, Minten C, van Vreden C, Ashhurst TM, Getts MT, Xie RD, Campbell IL, King NJ. Defective inflammatory monocyte development in IRF8-deficient mice abrogates migration to the West Nile virus-infected brain. J Innate Immun. 2015;7:102–112. doi: 10.1159/000365972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Wilensky A, Tzach-Nahman R, Potempa J, Shapira L, Nussbaum G. Porphyromonas gingivalis gingipains selectively reduce CD14 expression, leading to macrophage hyporesponsiveness to bacterial infection. J Innate Immun. 2015;7:127–135. doi: 10.1159/000365970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Ranjan R, Deng J, Chung S, Lee YG, Park GY, Xiao L, Joo M, Christman JW, Karpurapu M. The transcription factor nuclear factor of activated T cells c3 modulates the function of macrophages in sepsis. J Innate Immun. 2014;6:754–764. doi: 10.1159/000362647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Subramanian K, Winarsih I, Keerthani C, Ho B, Ding JL. Preferential silent survival of intracellular bacteria in hemoglobin-primed macrophages. J Innate Immun. 2014;6:515–529. doi: 10.1159/000358236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Márkus R, Lerner Z, Honti V, Csordás G, Zsámboki J, Cinege G, Párducz Á, Lukacsovich T, Kurucz É, Andó I. Multinucleated giant hemocytes are effector cells in cell-mediated immune responses of Drosophila. J Innate Immun. 2015;7:340–353. doi: 10.1159/000369618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Benard EL, Racz PI, Rougeot J, Nezhinsky AE, Verbeek FJ, Spaink HP, Meijer AH. Macrophage-expressed perforins mpeg1 and mpeg1.2 have an anti-bacterial function in zebrafish. J Innate Immun. 2015;7:136–152. doi: 10.1159/000366103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Mills CD, Ley K. M1 and M2 macrophages: the chicken and the egg of immunity. J Innate Immun. 2014;6:716–726. doi: 10.1159/000364945. [DOI] [PMC free article] [PubMed] [Google Scholar]