A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection

Cell Reports
Sarah E ClarkLaurel L Lenz

Abstract

The bacterial pathogen Listeria monocytogenes (Lm) capitalizes on natural killer (NK) cell production of regulatory interleukin (IL)-10 to establish severe systemic infections. Here, we identify regulators of this IL-10 secretion. We show that IL-18 signals to NK cells license their ability to produce IL-10. IL-18 acts independent of IL-12 and STAT4, which co-stimulate IFNγ secretion. Dendritic cell (DC) expression of Nlrp3 is required for IL-18 release in response to the Lm p60 virulence protein. Therefore, mice lacking Nlrp3, Il18, or Il18R fail to accumulate serum IL-10 and are highly resistant to systemic Lm infection. We further show that cells expressing or dependent on Batf3 are required for IL-18-inducing IL-10 production observed in infected mice. These findings explain how Il18 and Batf3 promote susceptibility to bacterial infection and demonstrate the ability of Lm to exploit NLRP3 for the promotion of regulatory NK cell activity.

Citations

Apr 26, 2020·Cancer Immunology, Immunotherapy : CII·Naoto OkaHaruki Okamura
Sep 26, 2019·Frontiers in Immunology·Sarah E ClarkLaurel L Lenz
Oct 24, 2020·Journal of Leukocyte Biology·Norberto W ZwirnerMercedes B Fuertes
Dec 29, 2020·Frontiers in Immunology·Sandy R LarsonLaurel L Lenz
Jun 8, 2019·Current Opinion in Immunology·Susan M BrewerDenise M Monack
Apr 17, 2021·Frontiers in Immunology·Hui SunBing Ni
May 28, 2019·Microbiology Spectrum·Sarah E F D'Orazio
Aug 3, 2021·Current Research in Immunology·Emily M EshlemanLaurel L Lenz
Dec 7, 2021·Frontiers in Cell and Developmental Biology·Yu GuoXiaopeng Qi

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