HDL Acts As An Opsonin Enhancing The Phagocytosis Of Group A Streptococcus By Monocyte

One of the main functions of high-density lipoprotein (HDL) is to transport cholesterol from the cells and tissue back to the liver for metabolism, which plays an important role in the process of removing cholesterol. However, accumulating evidence suggests that HDL help with disinfection.Recently, we demonstrated that HDL could specifically bind to Streptococcal collagen-like protein 1 (Sell) of M41-type group A Streptococcus (GAS). However, the pathological or physiological significance of Scll-HDL interaction is unknown. Therefore, we hypothesized that HDL might be act as an opsonin enhancing the phagocytosis of HDL-bound GAS by monocyte since some scavenger receptors can mediate the endocytosis of HDL. To validation the assumption, FITC-labeled bacteria, human U937 monocytes were used in analysis of phagocytosis. Colony counting, fluorescence intensity detection were employed to calculate the phagocytosis degree. The result showed that LDL (10μg/ml) and HDL (10μg/ml) could significantly accelerate U937 cell to endocytose M41 (ATCC 12373, AM41)-type GAS, and the phagocytosis rates after 60min incubation were increased by 55.2% and 20-30%, respectively, compared with LDL-free group and HDL-free group. The internalized GAS was found to be dead after 60min incubation with U937 cells either in the presence or absence of LDL and HDL. Results indicated that the phagocytic capacity of LDL mediated U937 monocyte is the strongest, followed by HDL. Although very-low-density lipoprotein (VLDL) could specifically bind with M41 (ATCC 12373, AM41)-type GAS VLDL had no opsonization. On the other hand, LDL, HDL, VLDL did not enhance the phagosytosis of M41 (CMCC 32198, CM41)-type GAS since the strain did not bind to LDL, HDL and VLDL.Moreover, physiological concentration of HDL (1000μg/ml) also has a similar effect. CD36 was the major scavenger receptor mediating the uptake of HDL-bound GAS by monocyte U937 cells since anti-CD36 antibody completely abolished opsonic phagocytosis but anti-CD4 antibody did not. Therefore, mononuclear cell surface receptor CD36 is involved in the opsonophagocytosis. Futhermore, recombinant Streptococcal collagen-like protein 1 (rScll), derived from M41-type GAS, could significantly decrease the opsonophagocytosis of AM41 but not CM41-type GAS since the rScll competitively blocked the interaction of AM41-type GAS with HDL. Therefore, our findings suggest that HDL may be an opsonin to enhance CD36-dependent opsonic phagocytosis of GAS by monocyte.