Marginal Zone B Cell Is a Major Source of Il-10 inListeria monocytogenesSusceptibility

Abstract

Rag-1-knockout (KO) mice are highly resistant to Listeria monocytogenes infection. The role played by the many Rag-1-dependent lymphocyte lineages was studied using a genetic approach in which each Rag-1-dependent lymphocyte lineage was eliminated one at a time. Only B cell-deficient Igh-KO mice displayed reduced bacterial load and improved survival upon Listeria infection. Listeria infection of Rag-1-KO and Il-10-KO hosts that had been adoptively transferred with wild-type marginal zone B (MZB) cells, but not follicular B cells, resulted in heightened bacterial load and increased Il-10 production in the spleen, but not the liver. This MZB cell-dependent increase in bacterial load was eliminated by anti-Il-10 mAb. In addition, Listeria infection of MZB cell-deficient Rbpj-cKO mice showed decreased bacterial load and increased survival. Whereas multiple cell types have been shown to be capable of Il-10 production, our results indicate that the MZB cell is the most dominant and relevant Il-10 source in the context of Listeria susceptibility. In marked contrast to the generally protective nature of MZB cells in defending against pathogenic infection, our results demonstrate that MZB cells play a detrimental role in Listeria infection and possibly other infections as well.

Antibody-independent functions of B cells: a focus on cytokines

“…Indeed, this has been confirmed in mice infected with S. Typhimurium or L. monocytogenes 78,104,105 .…”

“…B cells show similar suppressive roles during L. monocytogenes infection 105 . Compared with controls, B cell-deficient mice show increased resistance to L. monocytogenes infection, as shown by their lower bacterial loads in the spleen and liver, as well as by their improved survival rates following infection 105 .…”

“…Compared with controls, B cell-deficient mice show increased resistance to L. monocytogenes infection, as shown by their lower bacterial loads in the spleen and liver, as well as by their improved survival rates following infection 105 . The negative effect of B cells could be recapitulated by adoptive transfer of marginal zone B cells, which were the most efficient IL-10-producing B cell subset on exposure to L. monocytogenes in vitro 105 and which inhibited the resistance of recipient V(D)J recombinationactivating protein (RAG)-or IL-10-deficient mice in an IL-10-dependent manner 105 . Thus, IL-10-producing B cells interfere with innate defence mechanisms.…”

Regulatory functions of innate-like B cells

“…MZ B cell-derived IL-10 inhibited innate immunity and increased the host's susceptibility to Listeria infection. 55 …”

The adaptor ASC exacerbates lethal Listeria monocytogenes infection by mediating IL‐18 production in an inflammasome‐dependent and ‐independent manner

“…5C), it appears IL-10 has an immunosuppressive effect in both organs during severe listeriosis. It has been demonstrated that B cells are important for IL-10 production in the spleen, but not in the liver, during L. monocytogenes infection [43], suggesting that the mechanisms involved in IL-10 production are different between the organs, which may explain the liver-specific role of ASC, IL-18, and NK cells in exacerbating lethal L. monocytogenes infection. While ASC is an inflammasome adaptor, inflammasomeindependent roles of ASC have been documented in recent studies [29,44,45] Eur.…”