Department of Biology and Center for Life in Extreme Environments, Portland State University, Portland, Oregon, United States of America.
PLoS Pathog. 2022 Aug 4;18(8):e1010657. doi: 10.1371/journal.ppat.1010657. eCollection 2022 Aug.
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.
补体途径的激活导致生物活性 C3a 的产生，这是 C3 裂解的产物，与膜结合受体 C3aR 相互作用，调节先天免疫细胞的功能和细菌感染的结果。具体来说，先前的研究已经确定了 C3aR 在调节先天免疫细胞炎症状态、抗菌杀伤能力和代谢方面具有机制上不同和细胞类型特异性的作用。从历史上看，C3a 的产生局限于血清中；然而，最近的研究提供了证据，表明各种细胞类型可以产生刺激细胞内 C3aR 的细胞内 C3a。鉴于这些新的结果，我们有必要重新审视以前关于 C3aR 在控制细菌感染中的作用的研究，并在细胞外和细胞内 C3a 产生和 C3aR 激活的背景下分析这些结果。因此，这篇综述将涵盖 C3aR 在驱动细菌感染期间细胞类型特异性和组织特异性反应中的特定作用，并强调 C3a-C3aR 轴在调节宿主对细菌感染的抵抗力方面的贡献。
