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.