LFA-1 interaction with GBP-130 on-infected red blood cells mediates NK cell activation and parasite control

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Natural killer (NK) cells contribute to early immunity againstby recognizing and eliminating infected red blood cells (iRBCs), a process mediated in part by the integrin LFA-1. However, the cognate parasite ligand for LFA-1 has remained unknown. Here, we identify glycophorin binding protein-130 (GBP-130) as a surface-expressed ligand on iRBCs that binds the I-domain of LFA-1 (LFA-1 αI). Using an LFA-1 αI-Fc fusion protein, we demonstrate stage-specific binding to iRBCs, and LC-MS/MS analysis of immunoprecipitates of αI-Fc bound to iRBC revealedGBP-130 as a high-confidence interactor. RecombinantGBP-130 binds NK and THP-1 cells in an LFA-1-dependent manner. Co-culture assays show thatGBP-130 promotes NK cell activation and degranulation and facilitates contact-dependent killing of iRBCs. Neutralizing antibodies againstGBP-130 significantly impair these responses. Our findings establishGBP-130 as the LFA-1 ligand on iRBCs, providing new insight into NK cell-mediated immunity in malaria and identifying a potential target for host-directed interventions.