Interleukin-15 and NK1.1+ cells provide innate protection against acute Salmonella enterica serovar Typhimurium infection in the gut and in systemic tissues.

Control of bacterial colonization at mucosal surfaces depends on rapid activation of the innate immune system. Interleukin-15 (IL-15) directs the development, maturation, and function of a population of cells positive for NK1.1, such as natural killer (NK) cells, which are critical components of the innate immune defense against several viral and bacterial pathogens. Using IL-15-deficient mice, in vivo depletion of NK1.1(+) cells from wild-type mice, and in vivo overexpression of IL-15 from a recombinant adenovirus, we tested the role of IL-15 and NK1.1(+) cells in innate protection of the murine gut and reticuloendothelial system from Salmonella enterica serovar Typhimurium infection. IL-15 and the NK1.1(+) cell population provided innate protection from serovar Typhimurium in mice at the enteric mucosae and in the reticuloendothelial system during murine typhoid. Interestingly, serovar Typhimurium extensively colonized the gut of IL-15(-/-) mice and wild-type C57BL/6 mice depleted of NK1.1(+) cells prior to infection, even though the animals were not pretreated with antibiotics to reduce colonization resistance and there was an absence of overt inflammation in the colon and cecum. Enhanced dissemination of Salmonella from the gut of mice depleted of NK1.1(+) cells correlated with a localized disruption of IL-17 in the colon. These data suggest a relationship between the gut ecosystem and the innate mucosal immune system, which may be linked via IL-15 and NK1.1(+) cells.