Journal of leukocyte biology
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Class-A scavenger receptors (SR-A) and TLR mediate early immune responses against pathogenic bacteria. SR-A and TLR molecules are expressed on phagocytes and interact with common ligands from Gram-negative and Gram-positive bacteria; however, the contribution of TLR activity to SR-A-mediated phagocytosis has not been assessed directly. Herein, we provide genetic and functional evidence that ligand- and TLR-specific stimuli synergize with SR-A to mediate bacterial phagocytosis. ⋯ In support of this, we show that SR-A(+/-)MyD88(+/-) cells recapitulate the phagocytosis defect observed in SR-A(+/-)TLR4(+/-) cells. These data identify for the first time that TLR-driven innate immune responses, via a MyD88 signaling mechanism, regulate SR-A-dependent phagocytosis of bacteria. These findings provide novel insights into how innate immune cells control SR-A-mediated trafficking and are the first demonstration that subtle changes in the expression of SR-A and TLRs can substantially affect host bacterial clearance.