LDL Acts As An Opsonin Enhancing The Phagocytosis Of Group A Streptococcus By Monocyte/Macrophage

Low-density lipoprotein(LDL) binds to Streptococcal collagen-like protein(Sc11 protein) on the surface of group A Streptococcus, and scavenger receptor CD36 binds to and mediates the uptake of LDL by monocyte/macrophage. Therefore, we hypothesized that LDL might be an opsonin enhancing the phagocytosis of LDL-bound GAS by monocyte/magcrophage.Colony counting, fluorescence intensity detection and microscopic observation were used in phagocytosis assays to test the hypothesis. The results showed that LDL(10μg/mL) could significantly promote U937 cell to phagocytose M28(ATCC BAA1064) and AM41(ATCC 12373)-type GAS, and the phagocytosis rates after 30 min incubation were increased by 86.9% and 57.9%, respectively, compared with LDL-free group. LDL, however, did not enhance the phagosytosis of CM41(CMCC 32198) or M6(ATCC BAA946)-type GAS since these two strains did not bind to LDL. After one hour, LDL-mediated group and LDL-free group, GAS were killed by U937 mononuclear cells.Different concentrations of LDL from 10 μg/mL to 1000 μg/mL have no effect on the phagocytosis ability of the GAS by U937 mononuclear cells. CD36 was the major scavenger receptor mediating the uptake of LDL-bound GAS by monocyte U937 cells since anti-CD36 antibody abolished opsonic phagocytosis but anti-CD4 antibody did not. Moreover, recombinant Streptococcal collagen-like protein 1(r Scl1) derived from M41-type GAS could significantly decrease the opsonophagocytosis of AM41-type GAS 27.1%, because the rScl1 competitively blocked the binding of AM41-type GAS to LDL.69% of AM41-type GAS cells were killed in human blood after 15-min incubation whereas 16% of CM41-type GAS were phagocytosed. Recombinant Streptococcal collagen-like protein 1(r Scl1) derived from M41-type GAS could significantly decrease the opsonophagocytosis of AM41-type GAS by 74.5% but not CM41-type GAS, because the rScl1 competitively blocked the binding of AM41-type GAS to LDL. Futhermore, LDL was demonstrated to enhance the phagocytosis of AM41-type GAS but not CM41-type GAS by U937 cell-differentiated macrophage.On a conclusion, LDL can act as an opsonin to enhance CD36-dependent opsonic phagocytosis of GAS by U937 cells. To the best of our knowledge, it is the first time that LDL is demonstrated to be an opsonin, and CD36 acts as an opsonin receptor. Our findings may be an important addition to the field of immunology, may also shed a new light on the correlation of infection and atherosclerosis.