The Janus face of macrophages in immunity.

In 1882, Ilya Mechnikov discovered the phenomenon of phagocytosis when he studied larvae of starfishes that were present on small thorns from a tangerine tree that had been prepared for Christmas. The next morning he found the thorns surrounded by the mobile cells. Knowing that when inflammation occurs in animals that have a blood vascular system leukocytes escape from their blood vessels, it occurred to him that these cells might take up and digest bacteria that infest the body [1] . Since their discovery, the knowledge concerning macrophage subsets, functions and roles in health and disease has become comprehensive and sometimes difficult to grasp, in particular for the non-expert. The field became even more complex with the entrance of dendritic cells (DCs). It took Ralph Steinman and Zanvil Cohn [2] , who first described DCs in 1973, many years to convince the immunology community that these cells were truly distinct from macrophages. Distinguishing DCs from macrophages is still a matter of debate, and the heterogeneity of the mononuclear phagocyte system was recently reviewed [3] . In this issue, Charles D. Mills and Klaus Ley [4] present an excellent review on the biology of M1 and M2 macrophages, providing perspectives that help to better understand this complex field. Their reasoning centers around ‘inhibit’-type macrophages (M1) can rapidly kill pathogens and are thus primary in host defense while ‘heal’-type macrophages (M2) repair and maintain tissue integrity. Even early forms of life have features of macrophages, for example amoebas that can phagocytose foreign objects but also have the ability to repair [5] . Macrophages are the most numerous leukocytes throughout the animal kingdom and originate from several places including the fetal yolk sac, local renewal, and are also recruited from bone marrow-derived monocytes [6–9] . In the different compartments of the spleen, macrophage populations can be Published online: September 10, 2014 Journal of Innate Immunity