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J Exp Med. B cells enhance early innate immune responses during bacterial sepsis
[Source: Journal of Experimental Medicine, full text: (LINK). Abstract, edited.]
B cells enhance early innate immune responses during bacterial sepsis
Kelly-Scumpia, K. M., Scumpia, P. O., Weinstein, J. S., Delano, M. J., Cuenca, A. G., Nacionales, D. C., Wynn, J. L., Lee, P. Y., Kumagai, Y., Efron, P. A., Akira, S., Wasserfall, C., Atkinson, M. A., Moldawer, L. L.
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<SUP>?/?</SUP> 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<SUP>?/?</SUP> 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<SUP>?/?</SUP> mice with WT, but not IFNAR<SUP>?/?</SUP>, 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.
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Kelly-Scumpia, K. M., Scumpia, P. O., Weinstein, J. S., Delano, M. J., Cuenca, A. G., Nacionales, D. C., Wynn, J. L., Lee, P. Y., Kumagai, Y., Efron, P. A., Akira, S., Wasserfall, C., Atkinson, M. A., Moldawer, L. L.
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<SUP>?/?</SUP> 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<SUP>?/?</SUP> 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<SUP>?/?</SUP> mice with WT, but not IFNAR<SUP>?/?</SUP>, 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.