Scavenger receptor A1 participates in the phagocytosis ofLeptospira interrogansand leads to subsequent high inflammatory responses and bacterial dissemination in leptospirosis

Leptospirosis, caused by pathogenicLeptospiraspecies, has emerged as a widespread zoonotic disease worldwide. Macrophages mediate the elimination of pathogens through phagocytosis and cytokine production. Scavenger receptor A1 (SR-A1), one of the critical receptors mediating this process, plays a complicated role in innate immunity. However, the role of SR-A1 in the immune response against pathogenicLeptospirainvasion is unknown. In the present study, we found that SR-A1 is an important nonopsonic phagocytic receptor on murine macrophages forLeptospira. We also found that leptospiral LPS is the ligand of SR-A1. However, intraperitoneal injection of leptospires into WT mice presented with more severe jaundice, subcutaneous hemorrhaging, and higher bacteria burdens in blood and tissues than that of SR-A1-/-mice. Exacerbated cytokine and inflammatory mediator levels were also observed in WT mice and higher recruited macrophages in the liver than those of SR-A1-/-mice. Our findings collectively reveal that although beneficial in the uptake ofLeptospiraby macrophage, SR-A1 might be exploited byLeptospirato promote bacterial dissemination and modulate inflammatory activation, which causes a more severe infection in the host. These results provide our new insights into the innate immune response during early infection byL. interrogans.