Response to microbial infection must be perfectly balanced to kill off the bugs but not the surrounding host tissue. Wirtz et al. (page 1875) report that in sepsis this balance fails. By attempting to prevent an overzealous innate immune response, the cytokine IL-27 prevents efficient bacterial clearance.
IL-27 is strongly induced by microbial stimuli in vitro, but its response to microbes in vivo was unclear. In a mouse model of septic peritonitis, microbial invasion from the gut triggered IL-27 production. IL-27 was produced earlier than cytokines of the adaptive immune response, IL-12 and IL-23, indicating that IL-27 induction was, in this case, part of the innate response.
In earlier studies, IL-27 was shown to promote T cell proliferation and thus positively regulate adaptive immunity. In the present study, however, IL-27 displayed a negative effect on the innate response: mice lacking functional IL-27 cleared...
