Conventional NK Cells Can Produce IL-22 and Promote Host Defense in Klebsiella pneumoniae Pneumonia

It was reported that host defense against pulmonary Klebsiella pneumoniae infection requires IL-22, which was proposed to be of T cell origin. Supporting a role for IL-22, we found that Il22 −/− mice had decreased survival compared with wild-type mice after intratracheal infection with K. pneumoniae. Surprisingly, however, Rag2 −/− mice did not differ from wild-type mice in survival or levels of IL-22 in the lungs postinfection with K. pneumoniae. In contrast, K. pneumoniae –infected Rag2 −/− Il2rg −/− mice failed to produce IL-22. These data suggested a possible role for NK cells or other innate lymphoid cells in host defense and production of IL-22. Unlike NK cell–like innate lymphoid cells that produce IL-22 and display a surface phenotype of NK1.1 − NKp46 + CCR6 + , lung NK cells showed the conventional phenotype, NK1.1 + NKp46 + CCR6 − . Mice depleted of NK cells using anti–asialo GM1 showed decreased survival and higher lung bacterial counts, as well as increased dissemination of K. pneumoniae to blood and liver, compared with control-treated mice. NK cell depletion also led to decreased production of IL-22 in the lung. Within 1 d postinfection, although there was no increase in the number of lung NK cells, a subset of lung NK cells became competent to produce IL-22, and such cells were found in both wild-type and Rag2 −/− mice. Our data suggest that, during pulmonary infection of mice with K. pneumoniae , conventional NK cells are required for optimal host defense, which includes the production of IL-22.