biostudies-literatureYang SWKorea Health Industry Development InstituteNational Research Foundation of Korea133https://www.ebi.ac.uk/biostudies/studies/S-EPMC6733876biostudies-literatureUnknown5Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against <i>Streptococcus pneumoniae</i>. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against <i>S. pneumoniae</i>, thus facilitating rapid clearance of the pathogen. TheCell death discoveryDominant role of splenic marginal zone lipid rafts in the classical complement pathway against <i>S. pneumoniae</i>.PMC6733876S201803S00049HI17C1713NRF2017R1C1B2010487Choi HYun TJPark MLee YKJoo JSJin YYang SWChoi ISPark JYChoi WSKim MKPark SHHwang HSKang YSfalseDominant role of splenic marginal zone lipid rafts in the classical complement pathway against <i>S. pneumoniae</i>.Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway against <i>Streptococcus pneumoniae</i>. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway against <i>S. pneumoniae</i>, thus facilitating rapid clearance of the pathogen. The2019-01-01T00:00:00Z20192025-04-04T08:29:48.402Z2019-09-24T07:09:10ZS-EPMC67338763153123110.1038/s41420-019-0213-3