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

Abstract

It has been reported that host defense against pulmonary K. pneumoniae infection requires IL-22, which has been proposed to be of T cell origin. Supporting a role for IL-22, we found that Il22−/− mice had decreased survival as 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 after infection with K. pneumoniae. By 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 (ILC) in host defense and production of IL-22. Unlike NK cell-like ILCs 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 as compared with control-treated mice. NK cell depletion also led to decreased production of IL-22 in the lung. Within one day after infection, 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.

Th17 Differentiation and Their Pro-inflammation Function

“…The combination of IL-22 with IL-17 also induced several pro-inflammatory cytokines and chemokines or antimicrobial peptides expression in lung epithelial cells [10]. Another study also found that, comparing with wild-type mice, Il22-deficient mice died quickly after Klebsiella pneumoniae infection [301]. As described above, after Citrobacter rodentium infection, deficiency of IL-22 in mice led to increased intestinal damage, bacterial load and mortality [325].…”

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…Both Th17 and Th22 cells were initially thought to be the origin of IL-22 during K. pneumoniae infection (184). However, since recent work has shown that ␣␤ T cells are unnecessary for the control of infection (184), while NK cells both promote the survival of mice during K. pneumoniae pneumonia and produce IL-22 (189), it is now thought that NK cells are the major source of IL-22 and are critical for controlling K. pneumoniae infections in lungs. Another innate lymphoid cell type, mucosa-associated invariant T (MAIT) cells, has also been suggested to play a nonredundant role in controlling infection, particularly in the K. pneumoniae peritonitis model (184,190,191).…”

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

“…Similarly, CD8 + T cells have been shown to provide resilience in response to influenza and RSV infections, as sources of IL-10, which curbs lung injury (119); such roles of CD8 + T cells outside of viral infection remain less certain. NK cells are sources of IL-22 and its contributions to resilience during K. pneumoniae or influenza pneumonia (100, 120). A novel set of tissue-protective lymphocytes was identified during influenza infection as a population of lineage-negative CD90 + CD25 + innate lymphoid cells that promote resilience through expression of the EGF family member amphiregulin (121).…”