The Toll-like receptors (TLRs) and complement are key innate defense systems that are triggered rapidly upon infection. Although both systems have been investigated primarily as separate entities, an emerging body of evidence indicates extensive crosstalk between complement and TLR signaling pathways. Analysis of these data suggests that the complement-TLR interplay reinforces innate immunity or regulates excessive inflammation, through synergistic or antagonistic interactions, respectively. However, the facility of complement and TLRs for communication is exploited by certain pathogens as a means to modify the host response in ways that favor the persistence of the pathogens. Further elucidation of regulatory links between complement and TLRs is essential for understanding their complex roles in health and disease.
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