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IL-22: a balancing act of microbes in the inflamed gut
▸ Behnsen J, Jellbauer S, Wong CP, et al. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 2014;40:262–73.
IL-22 is produced by immune cells in response to pathogenic infection. One of the ways that IL-22 is thought to enhance the mucosal barrier is through the induction of antimicrobial proteins. Although IL-22 promotes epithelial antimicrobial defences, many pathogens, such as Salmonella, colonise mucosal surfaces and establish infection. The way in which Salmonella outcompetes the microbiota is not well understood. In this study, the authors investigate the role of IL-22 in the gut of mice during Salmonella infection. IL-22−/− mice orally infected with Salmonella were colonised less by this bacteria than infected wild-type (WT) mice, and this was rescued by injecting infected IL-22−/− mice with IL-22. The differences in levels of pathogen colonisation were not explained by degree of inflammation in the mice. There were no significant differences in the gut microbiome compositions of uninfected IL-22−/− and WT mice; however, there was a considerable difference in the relative abundance of Salmonella and Escherichia coli in the guts of inflamed mice. Salmonella contributed to approximately half of the total bacteria in infected WT mice, whereas E coli was only around 9%. In IL-22−/− mice, Salmonella only made up 15%, whereas E coli constituted about 40% of total bacteria. IL-22 was found to induce the expression of antimicrobial proteins, including lipocalin-2 and calprotectin, which sequester essential metal ions from microbes. Salmonella possess many virulence mechanisms that mediate resistance to specific microbial proteins and allow it to thrive in the inflamed gut. The authors discovered that Salmonella exploits IL-22 by expressing virulence factors that allow it to sequester essential nutrients and outcompete commensal Enterobacteriaceae, its closest relative in the intestine. This study is the first to …