September 2022
"Activation of the complement pathway results in the production of bioactive C3a, a product of C3 cleavage, which interacts with membrane-bound receptor C3aR to regulate innate immune cell function and outcome of bacterial infection. Specifically, previous research has identified mechanistically distinct and cell type–specific roles for C3aR in regulating innate immune cell inflammatory state, antimicrobial killing capacity, and metabolism. Historically, the production of C3a has been relegated to the serum; however, recent studies have provided evidence that various cell types can produce intracellular C3a that stimulates intracellular C3aR. In light of these new results, it is imperative that we revisit previous studies regarding the role of C3aR in controlling bacterial infections and analyze these results in the context of both extracellular and intracellular C3a production and C3aR activation. Thus, this review will cover specific roles of C3aR in driving cell type–specific and tissue specific responses during bacterial infections and emphasize the contribution of the C3a–C3aR axis in regulating host resistance to bacterial infection."