Scavenger receptor A1 participates in uptake of Leptospira interrogans serovar Autumnalis strain 56606v and inflammation in mouse macrophages

Leptospirosis, caused by pathogenic Leptospira species, 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 pathogenic Leptospira invasion is unknown. In the present study, we found that SR-A1 is an important nonopsonic phagocytic receptor on murine macrophages for Leptospira. However, intraperitoneal injection of leptospires into WT mice presented with more apparent 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 of Leptospira by macrophage, SR-A1 might be exploited by Leptospira to modulate inflammatory activation and increase the susceptibility of infection in the host. These results provide our new insights into the innate immune response during early infection by L. interrogans.