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.
Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Xin
X
Xu
Ido D
ID
Weiss
Hongwei H
HH
Zhang
Satya P
SP
Singh
Thomas A
TA
Wynn
Mark S
MS
Wilson
Joshua M
JM
Farber
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005260:Female; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D007710:Klebsiella Infections / Q000276:immunology* / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000401:mortality; D054399:Receptors, CCR6 / Q000378:metabolism; D013534:Survival; D000097043:Interleukin-22
D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; D007378:Interleukins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055627:Natural Cytotoxicity Triggering Receptor 1; D054399:Receptors, CCR6; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C507942:Il2rg protein, mouse; C527211:Klrb1c protein, mouse; C118384:Ncr1 protein, mouse; C499308:Rag2 protein, mouse