Bacteria and phagocytes: mortal enemies.

The research presented in this issue finds historical resonance in a classical scientific debate. Russian biologist Ilya Metchnikoff [1, 2] was awarded the Nobel Prize in 1908 for the development of the phagocyte theory, the central tenet of which was that the ‘swallowing and digestion’ of bacteria by circulating ‘white corpuscles’ (neutrophils and macrophages), enhanced by prior opsonization, provided immunity to infection [1–3] . However, a contemporary of Metchnikoff [1, 2] , the hygienist and bacteriologist Oskar Bail [4] , who was working at the German University (today named Charles University) in Prague, was simultaneously developing a countering ‘aggressin doctrine’. This model cautioned that many pathogens, including S. aureus , pneumococcus, the tubercle bacillus, or cholera, were able to effectively neutralize phagocytes by paralysis of function or dissolution of the host cell, all through the action of specific ‘aggressin’ molecules induced and released during the course of infection. Metchnikoff [5] made a specific point in his Nobel Prize acceptance speech to trivialize Bail’s [4] research: ‘Numerous findings, achieved with care over the last few years, clean contradict this view. It has been shown that the white corpuscles entertain no fear of microbial poisons and are well fitted to absorb them and make them harmless.’ As illustrated in this issue, the modern era of molecular microbiology has provided genetic approaches to pinpoint specific bacterial factors that fulfill the criteria of ‘aggressin’ proposed by Bail [4] – we can hope to the satisfaction rather than the chagrin of Metchnikoff ’s [1, 2] legacy. A critical first-line element of mammalian innate immunity is the function of phagocytic cells, in particular neutrophils and macrophages. The effectiveness of these specialized leukocytes in host defense reflects their capacity for directed migration, microbial uptake, and intraand extracellular microbial killing; the latter is achieved through the concerted action of reactive oxygen species, enzymatic proteolysis, and cationic antimicrobial peptides. Stimulated phagocytes also amplify inflammatory and immune responses through the release of cytokines, nitric oxide, and vasoactive peptides. Their general importance is further exemplified by the increased susceptibility to invasive bacterial infection in patients whose phagocyte numbers are markedly reduced. However, it is also apparent that several leading bacterial pathogens such as Staphylococcus aureus , Streptococcus pyogenes , and others are capable of causing severe invasive infections even in previously healthy individuals. Such intrinsic disease-producing capacity defines a superior ability of these pathogens to resist host phagocytic clearance through the coordinated expression of virulence determinants that interfere with phagocyte trafficking or opsonophagocytosis, or instead to neutralize the molecular effectors of bacterial killing. This special thematic issue of the Journal of Innate Immunity focuses on the elucidation of new bacterial virulence factors that target phagocyte defense pathways, pointing out the significant consequences they hold for the pathogen-host encounter. Published online: September 10, 2010 Journal of Innate Immunity