IL-18 from Batf3-dependent cells licenses natural killer cell IL-10 production during Listeria monocytogenes infection

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.114-114.1
• Main Authors: Clark, Sarah E., Schmidt, Rebecca L., McDermott, Daniel S., Lenz, Laurel L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.114.1

Natural killer (NK) cells are innate lymphoid cells that regulate the immune response to infection through secretion of both pro- and anti-inflammatory cytokines. The pathogen Listeria monocytogenes (Lm) capitalizes on NK cell production of the anti-inflammatory cytokine interleukin (IL)-10 during establishment of severe infection. Lm-stimulated NK cell IL-10 limits immune cell recruitment and activation, allowing for bacterial expansion. Here, we report that IL-18 from dendritic cells (DCs) promotes this IL-10 production. IL-18 acts directly on NK cells to license IL-10 secretion that is independent of IL-12 and STAT4, which co-stimulate IFNγ secretion during Lm infection and can induce NK cell IL-10 in other contexts. DC release of IL-18 is driven by the Lm p60 virulence protein and requires DC expression of nlrp3 and batf3. Mice lacking nlrp3, il18, il18R, or batf3 fail to accumulate serum IL-10 and are highly resistant to systemic Lm infection. Our data thus show that during systemic infection Lm selectively targets Baft3-dependent cells to drive IL-18 release that licenses NK cell IL-10 production. Exploiting this previously-unappreciated pathway to promote IL-10 production enables Lm to dampen inflammatory and anti-microbial host responses.