IL-33 receptor ST2 amplifies the expansion of NK cells and enhances host defense during mouse cytomegalovirus infection.
NK cells provide important host defense against viruses and can differentiate into self-renewing memory NK cells after infection, alloantigen stimulation, and cytokine stimulation. In this study, we investigated the role of the IL-33 receptor ST2 in the differentiation of NK cells during mouse CMV (MCMV) infection. Although ST2-deficient (Il1rl1 (-/-)) Ly49H(+) NK cells develop normally and differentiate into memory cells after MCMV infection, naive and memory Il1rl1 (-/-) Ly49H(+) NK cells exhibited profound defects in MCMV-specific expansion, resulting in impaired protection against MCMV challenge. Additionally, IL-33 enhanced m157 Ag-specific proliferation of Ly49H(+) NK cells in vitro. Thus, an IL-33/ST2 signaling axis in NK cells contributes to host defense against MCMV.
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143; Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan; and.
Tsukasa
T
Nabekura
Centre National de la Recherche Scientifique and Université de Toulouse, Institut de Pharmacologie et de Biologie Structurale, F-31077 Toulouse, France.
Jean-Philippe
JP
Girard
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143; Lewis.Lanier@ucsf.edu.
Lewis L
LL
Lanier
D000818:Animals; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D010641:Phenotype; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin