Unknown,Transcriptomics,Genomics,Proteomics

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Lack of Toll-like Receptor Signaling Improves Host Defense in Severe Septic Peritonitis in Severe Septic Peritonitis


ABSTRACT: TLRs are considered important for innate immune responses that combat bacterial infections. Here, the role of TLRs in severe septic peritonitis using the colon ascendens stent peritonitis (CASP) model was examined. We demonstrate that mice deficient for MyD88 and TRIF had markedly reduced bacterial numbers both in peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is inhibited by TLR signals. Moreover, survival of Myd88-/-;TrifLps2/Lps2 mice was significantly improved. The lack of TLR signals prevented the excessive induction of inflammatory cytokines and of IL 10. Notably, the expression of IFN-gamma, which has an essential protective role in septic peritonitis, and of IFN-regulated genes including several p47 and p65 GTPases as well as IP 10 was independent of TLR signaling. These results provide evidence that, in severe septic peritonitis, TLR deficiency balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN-gamma production. In this dataset, expression data of genes induced by septic peritonitis in spleens from TLR-deficient and wildtype mice are included. 3 groups (septic TLR-deficient mice, septic wildtype mice, and untreated wildtype mice) with 4 replicates each.

ORGANISM(S): Mus musculus

SUBMITTER: Olivia Prazeres da Costa 

PROVIDER: E-GEOD-24327 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Improved host defense against septic peritonitis in mice lacking MyD88 and TRIF is linked to a normal interferon response.

Reim Daniel D   Rossmann-Bloeck Tanja T   Jusek Gabriela G   Prazeres da Costa Olivia O   Holzmann Bernhard B  

Journal of leukocyte biology 20110531 3


The signaling adapters MyD88 and TRIF are engaged by TLRs and/or receptors of the IL-1 family and are considered important for innate immune responses that combat bacterial infections. Here, the consequences of a combined MyD88 and TRIF deficiency for the innate immune response against severe septic peritonitis was examined. We demonstrate that Myd88(-/-);Trif(Lps2/Lps2) mice had markedly reduced bacterial numbers in the peritoneal cavity and peripheral blood, indicating that bacterial clearance  ...[more]

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