Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-mediated signaling contributes to innate immune responses in the lung during Escherichia coli pneumonia

摘要: Bacterial pneumonia remains a serious disease and is associated with neutrophil recruitment. Innate immunity pivotal for the elimination of bacteria, TLRs are essential in this process. Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF) an TLR3 TLR4, MyD88-independent cascade. However, importance TRIF immune responses against pulmonary bacterial pathogens not well understood. We investigated involvement murine model Escherichia coli pneumonia. −/− mice infected E. display attenuated migration; NF-κB activation; TNF-α, IL-6, LPS-induced C-X-C chemokine production lungs. In addition, -induced phosphorylation JNK, ERK, p38 MAPK was detected bone marrow-derived macrophages (BMMs) +/+ mice, but BMMs mice. Furthermore, TNF-α IL-6 late activation, were abolished Moreover, required influx, keratinocyte cell-derived chemokine, MIP-2, Using we ruled out role TLR3-mediated TRIF-dependent influx during A TLR4-blocking Ab inhibited both suggesting that TRIF-mediated signaling involves TLR4. also found critical to control burden lungs dissemination. Thus, rapid activation TLR4-mediated cascade serves augment host defense Gram-negative pathogen.