期刊
EMBO JOURNAL
卷 31, 期 1, 页码 201-213出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2011.380
关键词
dendritic cells; sepsis; splenic macrophages; T cells; type I IFN
资金
- DFG [KFO115, SFB704]
Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis. The EMBO Journal (2012) 31, 201-213. doi: 10.1038/emboj.2011.380; Published online 28 October 2011
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