Type I interferon–responsive B cells provide early protection against bacterial sepsis

Akira, Shizuo

Atkinson, Mark A.

Cuenca, Alex G.

Delano, Matthew J.

Efron, Philip A.

Kelly-Scumpia, Kindra M.

Kumagai, Yutaro

Lee, Pui Y.

Moldawer, Lyle L.

Nacionales, Dina C.

Scumpia, Philip O.

Wasserfall, Clive

Weinstein, Jason S.

Wynn, James L.

English

PubMed

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

Kelly-Scumpia, Kindra M

Scumpia, Philip O

Weinstein, Jason S

Delano, Matthew J

Cuenca, Alex G

Nacionales, Dina C

Wynn, James L

Lee, Pui Y

Efron, Philip A

Atkinson, Mark A

Moldawer, Lyle L

eScholarship - University of California

B cells enhance early innate immune responses during bacterial sepsis

Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte.

CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.

CD4+ T cells induce innate responses independently of

Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis.

Integrin-mediated long-term B cell retention in the splenic marginal zone.

Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture.

MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis.

Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll-like receptors in immunity.

T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes.

Toll-like receptors control activation of adaptive immune responses.

Toll-like receptors: critical proteins linking innate and acquired

Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis.

Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3149216

B cells enhance early innate immune responses during bacterial sepsis

Abstract

Similar works

Full text

Available Versions

eScholarship - University of California