title: B cells enhance early innate immune responses during bacterial sepsis.
abstract: Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1(-/-) mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell-deficient or anti-CD20 B cell-depleted mice, but not α/β T cell-deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell-deficient mice with serum from wild-type (WT) mice and repletion of Rag1(-/-) mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1(-/-) mice with WT, but not IFNAR(-/-), B cells improves IFN-I-dependent and -independent early cytokine responses. Repleting B cell-deficient mice with the IFN-I-dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I-activated B cells in protective early innate immune responses during bacterial sepsis.
authors: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors: Kindra M
authors: KM
authors: Kelly-Scumpia
authors: Philip O
authors: PO
authors: Scumpia
authors: Jason S
authors: JS
authors: Weinstein
authors: Matthew J
authors: MJ
authors: Delano
authors: Alex G
authors: AG
authors: Cuenca
authors: Dina C
authors: DC
authors: Nacionales
authors: James L
authors: JL
authors: Wynn
authors: Pui Y
authors: PY
authors: Lee
authors: Yutaro
authors: Y
authors: Kumagai
authors: Philip A
authors: PA
authors: Efron
authors: Shizuo
authors: S
authors: Akira
authors: Clive
authors: C
authors: Wasserfall
authors: Mark A
authors: MA
authors: Atkinson
authors: Lyle L
authors: LL
authors: Moldawer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000276:immunology; D015169:Colony Count, Microbial; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000276:immunology; D018805:Sepsis / Q000276:immunology*
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D018398:Homeodomain Proteins; C508032:Ifnar1 protein, mouse; D051192:Receptors, Pattern Recognition; C064658:RAG-1 protein; D053633:Receptor, Interferon alpha-beta