MyD88 is an essential regulator of NK cell-mediated clearance of MCMV infection.

Autor: Dixon KJ; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Siebert JR; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Wang D; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Abel AM; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Johnson KE; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Riese MJ; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; Laboratory of Lymphocyte Signaling, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Terhune SS; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Tarakanova VL; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Thakar MS; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Malarkannan S; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. Electronic address: smalarkannan@versiti.org.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2021 Sep; Vol. 137, pp. 94-104. Date of Electronic Publication: 2021 Jul 06.
DOI: 10.1016/j.molimm.2021.07.001
Abstrakt: The signaling adapter MyD88 is critical for immune cell activation in response to viral or bacterial pathogens via several TLRs, IL-1βR and IL-18R. However, the essential role of MyD88 during activations mediated by germline-encoded NK cell receptors (NKRs), such as Ly49H or NKG2D, has yet to be investigated. To define the NK cell-intrinsic function of MyD88, we generated a novel NK cell conditional knockout mouse for MyD88 (Myd88 fl/fl Ncr1 Cre/+ ). Phenotypic characterization of these mice demonstrated that MyD88 is dispensable for NK cell development and maturation. However, the MyD88-deficient NK cells exhibited significantly reduced cytotoxic potentials in vivo. In addition, the lack of MyD88 significantly reduced the NKG2D-mediated inflammatory cytokine production in vitro. Consistent with this, mice lacking MyD88 were unable to respond and clear MCMV infection. Transcriptomic analyses of splenic NK cells following MCMV infection revealed that inflammatory gene signatures were upregulated in Ly49H + . In contrast, Ly49H - NK cells have significant enrichment in G2M checkpoint genes, revealing distinct transcriptomic profiles of these subsets. Our results identify a central role for MyD88 in Ly49H-dependent gene signatures, including alterations in genes regulating proliferation in Ly49H + NK cells. In summary, our study reveals a previously unknown function of MyD88 in Ly49H-dependent signaling and in vivo functions of NK cells.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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