title: Regulatory B cell (B10 Cell) expansion during Listeria infection governs innate and cellular immune responses in mice.
abstract: Pathogens use numerous methods to subvert host immune responses, including the modulation of host IL-10 production by diverse cell types. However, the B cell sources of IL-10 and their overall influence on innate and cellular immune responses have not been well characterized during infections. Using Listeria as a model pathogen, infection drove the acute expansion of a small subset of regulatory B cells (B10 cells) that potently suppress inflammation and autoimmunity through the production of IL-10. Unexpectedly, spleen bacteria loads were 92-97% lower in B10 cell-deficient CD19(-/-) mice, in mice depleted of mature B cells, and in mice treated with CD22 mAb to preferentially deplete B10 cells before infection. By contrast, the adoptive transfer of wild-type B10 cells reduced bacterial clearance by 38-fold in CD19(-/-) mice through IL-10-dependent pathways. B10 cell depletion using CD22 mAb significantly enhanced macrophage phagocytosis of Listeria and their production of IFN-γ, TNF-α, and NO ex vivo. Accelerated bacteria clearance following B10 cell depletion significantly reduced Ag-specific CD4(+) T cell proliferation and cytokine production, but did not alter CD8(+) T cell responses. B10 cell regulatory function during innate immune responses was nonetheless dependent on cognate interactions with CD4(+) T cells because B10 cells deficient in IL-10, MHC-II, or IL-21R expression did not influence Listeria clearance. Thus, Listeria manipulates immune responses through a strategy of immune evasion that involves the preferential expansion of endogenous B10 cells that regulate the magnitude and duration of both innate and cellular immune responses.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
authors.forename: Mayuka
authors.initials: M
authors.lastname: Horikawa
authors.forename: Eric T
authors.initials: ET
authors.lastname: Weimer
authors.forename: David J
authors.initials: DJ
authors.lastname: DiLillo
authors.forename: Guglielmo M
authors.initials: GM
authors.lastname: Venturi
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: Mark T
authors.initials: MT
authors.lastname: Heise
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018941:Antigens, CD19 / Q000235:genetics; D018951:Antigens, CD20 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D057131:Immune Evasion / Q000276:immunology*; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology* / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000096:biosynthesis / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000037:antagonists & inhibitors / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D018951:Antigens, CD20; C497868:Cd22 protein, mouse; C556062:IL10 protein, mouse; D051918:Sialic Acid Binding Ig-like Lectin 2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D010047:Ovalbumin