The year 2016 marks 100 years since the death of Élie Metchnikoff (1845–1916), the Russian zoologist who pioneered the study of cellular immunology and who is widely credited with the discovery of phagocytosis, for which he was jointly awarded the Nobel Prize in Physiology or Medicine in 1908. However, his long scientific career spanned many disciplines and has had far-reaching effects on modern immunology beyond the study of phagocytosis. In this Viewpoint article, five leading immunologists from the fields of phagocytosis, macrophage biology, leukocyte migration, the microbiota and intravital imaging tell Nature Reviews Immunology how Metchnikoff's work has influenced past, present and future research in their respective fields.
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Tauber, A. I. Metchnikoff and the phagocytosis theory. Nat. Rev. Mol. Cell. Biol. 4, 897–901 (2003).
Underhill, D. M. & Goodridge, H. S. Information processing during phagocytosis. Nat. Rev. Immunol. 12, 492–502 (2012).
Cosson, P. & Soldati, T. Eat, kill or die: when amoeba meets bacteria. Curr. Opin. Microbiol. 11, 271–276 (2008).
Metchnikoff, E. Lectures on the Comparative Pathology of Inflammation, Delivered at the Pasteur Institute in 1891 (Dover Publications, 1968).
Metchnikoff, E. Immunity in Infectious Diseases (Cambridge Univ. Press, 1905).
Tauber, A. I. & Chernyak, L. Metchnikoff and the Origins of Immunology. From Metaphor to Theory (Oxford Univ. Press, 1991).
Cohnheim, J. Neue Untersuchungen Über die Entzündung (in German) (August Hirschwald, 1873).
von Limbeck, R. R. The Clinical Pathology of the Blood (Harvard Univ. Press, 1901).
Metchnikoff, E. The Prolongation of Life. Optimistic Studies (G. P. Putnam's Sons, 1908).
Metchnikoff, E. Poisons intestinale et scléroses. Ann. Inst. Pasteur 24, 755–770 (in French) (1910).
Ginhoux, F. & Guillams, M. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44, 439–449 (2016).
Gordon, S. Phagocytosis: an immunobiologic process. Immunity 44, 463–475 (2016).
Yun, M. H., Davaapil, H. & Brockes, J. P. Recurrent turnover of senescent cells during regeneration of a complex structure. eLife 4, e05505 (2015).
Cash, J. L. & Martin, P. Myeloid cells in cutaneous wound repair. Microbiol. Spectr. http://dx.doi.org/10.1128/microbiolspec.MCHD-0017-2015 (2016).
Crotte, A. & Ransohoff, R. M. Microglial physiology and pathophysiology: insights from genome-wide transcriptional profiling. Immunity 44, 505–515 (2016).
Gordon, S. Elie Metchnikoff, the man and the myth. J. Innate Immun. 8, 223–227 (2016).
Gallatin, W. M., Weissman, I. L. & Butcher, E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature 304, 30–34 (1983).
Ley, K. in Handbook of Physiology. Microcirculation (eds Tuma, R. F., Duran, W. N. & Ley, K.) 387–448 (Elsevier, 2008).
Muller, W. A. Localized signals that regulate transendothelial migration. Curr. Opin. Immunol. 38, 24–29 (2016).
Nourshargh, S. & Alon, R. Leukocyte migration into inflamed tissues. Immunity 41, 694–707 (2014).
Griffith, J. W., Sokol, C. L. & Luster, A. D. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol. 32, 659–702 (2014).
Kulp, W. L. & Rettger, L. F. Comparative study of Lactobacillus acidophilus and Lactobacillus bulgaricus. J. Bacteriol. 9, 357–395 (1924).
Quigley, E. M. Gut microbiota and the role of probiotics in therapy. Curr. Opin. Pharmacol. 11, 593–603 (2011).
Sanders, M. E. et al. Health claims substantiation for probiotic and prebiotic products. Gut Microbes 2, 127–133 (2011).
Van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).
Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159–166 (2014).
Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).
Koeth, R. A. et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576–585 (2013).
Zhu, W. et al. Gut microbial metabolite TMAO enhances platelet hyperreactivy and thrombosis risk. Cell 165, 111–124 (2016).
Comandon, J. Mouvements des leucocytes quelques tactismes étudiés a l'aide de l'enregistrement cinématogrique. Ann. Inst. Pasteur 34, 1–24 (in French) (1920).
Dean, K. M. & Palmer, A. E. Advances in fluorescence labeling strategies for dynamic cellular imaging. Nat. Chem. Biol. 10, 512–523 (2014).
Germain, R. N., Robey, E. A. & Cahalan, M. D. A decade of imaging cellular motility and interaction dynamics in the immune system. Science 336, 1676–1681 (2012).
Cahalan, M. D. & Parker, I. Choreography of cell motility and interaction dynamics imaged by two-photon microscopy in lymphoid organs. Annu. Rev. Immunol. 26, 585–626 (2008).
Yang, Z. & Klionsky, D. J. Eaten alive: a history of macroautophagy. Nat. Cell Biol. 12, 814–822 (2010).
Munz, C. Of LAP, CUPS, and DRibbles – unconventional use of autophagy proteins for MHC restricted antigen presentation. Front. Immunol. 6, 200 (2015).
Gordon, S. Tissue macrophages: framing the questions. BMC Biol. (in the press).
Nourshargh, S., Renshaw, S. A. & Imhof, B. A. Reverse migration of neutrophils: where, when, how, and why? Trends Immunol. 37, 273–286 (2016).
Khanna, S. et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J. Infect. Dis. 214, 173–181 (2016).
Bousso, P. & Moreau, H. D. Functional immunoimaging: the revolution continues. Nat. Rev. Immunol. 12, 858–864 (2012).
Tischer, D. & Weiner, O. D. Illuminating cell signalling with optogenetic tools. Nat. Rev. Mol. Cell. Biol. 15, 551–558 (2014).
The work of B.A.I. was supported by Swiss National Science Foundation Grant 310030_153456.
The authors declare no competing financial interests.
About this article
Cite this article
Underhill, D., Gordon, S., Imhof, B. et al. Élie Metchnikoff (1845–1916): celebrating 100 years of cellular immunology and beyond. Nat Rev Immunol 16, 651–656 (2016). https://doi.org/10.1038/nri.2016.89
Frontiers in Immunology (2021)
The FEBS Journal (2021)
Type 2 diabetes mellitus-related environmental factors and the gut microbiota: emerging evidence and challenges
International Immunology (2020)
A transcriptome-based approach to identify functional modules within and across primary human immune cells
PLOS ONE (2020)