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- W4313359069 abstract "Abstract Background Toll like receptor 9 (TLR9) is identified as anintracellular DNA receptor playing important roles in immunity. However, the mechanisms of how TLR9 regulates host defense are unclear. B1 cells are aninnate-like B cell population predominately residing in peritoneum and highly express TLR9. Therefore, we hypothesize that TLR9 may regulate host defense via modulation of peritoneal B1 pathobiology during sepsis. Method C57BL/6 (WT) mice and TLR9−/− mice were subjected to cecal ligation and puncture (CLP) with for 18 hours. Result Deletion of TLR9 increased survival as well as decreased bacterial load and systemic inflammation after CLP. Interestingly, peritoneal B1 cell numbers were significantly higher in TLR9−/− than WT mice, associated with significant increases of peritoneal CXCL13 level in TLR9−/− miceat baseline and after CLP. Strikingly, the expression level of CXCL13, a B cell-attracting chemokine, in the mesenteric adipo tissue was 50 fold higher inTLR9−/− than WT mice after CLP. Treatment with CXCL13 neutralizing antibody impaired bacterial clearance and decreased peritoneal B1 cell numbersin TLR9−/− mice compared to the IgG control after CLP, suggesting that TLR9 regulated B1 cell recruitment via CXCL13. Furthermore, deletion of TLR9 significantly increased peritoneal natural antibody IgM levels compared to WT at baseline and after CLP. Importantly, adoptive transfer of TLR9−/−B1 cells to WT mice improved bacterial clearance and increased peritoneal IgM levels compared to adoptive transfer of WT B1 cells after CLP. Conclusions These findings revealed an unrecognized role of TLR9 in modulating host defense via regulating B1 cell recruitment and IgM production during intra-abdominal sepsis." @default.
- W4313359069 created "2023-01-06" @default.
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- W4313359069 date "2018-05-01" @default.
- W4313359069 modified "2023-10-18" @default.
- W4313359069 title "TLR9 regulates host defense via modulation of peritoneal B1 cell recruitment and functions during intra-abdominal sepsis." @default.
- W4313359069 doi "https://doi.org/10.4049/jimmunol.200.supp.114.8" @default.
- W4313359069 hasPublicationYear "2018" @default.
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