Sepsis and evolution of the innate immune response

Objective: To review the role of the Toll-like receptors (TLR) as the principal sensors used by the innate immune system in the context of the pathologic processes underlying sepsis and septic shock. Data Sources: Literature review. Data Summary: Through the Toll-like receptors, macrophages and other defensive cells "see" endotoxin (TLR4), peptidoglycan (TLR2), and bacterial DNA (TLR9). Representatives of the family predated the divergence of plants and animals and, at that time, had already acquired a defensive function. The strengths and liabilities of the innate immune system, which defends against infection and which also may cause shock and death, are rooted in its ancient origins. In the current era of shock research, the nature of the signals that Toll-like receptors transduce and the effects of genetic variation on microbial sensing are two major challenges.