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

Abstract

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.

Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis

“…Liver macrophages are divided into two distinct populations, liver resident macrophages from the fetal yolk sac called Kupffer cells (KCs) and monocyte-derived macrophages (MDMs) from the blood. These macrophages can mediate the clearance of apoptotic cells and foreign pathogens through phagocytosis and cytokine production ( 10 ). Notably, they are also the primary regulators of the inflammatory response.…”

“…MSR1 is mainly expressed on macrophages and dendritic cells, and recent studies have found that MSR1 is also present on the surface of lymphocytes and may be involved in the pathogenesis of asthma and chronic obstructive pulmonary disease ( 23 ). Since macrophages mediate pathogen elimination through phagocytosis and cytokine production, MSR1 expression is important for the elimination of foreign pathogens ( 10 ). LPS is an important endogenous deleterious agent, and TLR4 is the main ligand of LPS, MSR1 and TLR4 cooperation can activate phagocytosis of the Gram-negative bacterium Escherichia coli , while MSR1 interacts with TLR2 to promote phagocytosis of the Gram-negative bacterium Staphylococcus aureus ( 24 ).…”