LFA-1 Interaction with GBP-130 on Plasmodium falciparum-infected Red Blood Cells mediates NK Cell Activation and Parasite Control
Mukhtar, O.; Dutt, R.; Panda, A.; Kumari, P.; Singh, S. S.; Paul, G.; Prakash, N.; Abbas, M.; Islam, M. M.; Arora, P.; Mohmmed, A.; Kumar, D.; Malhotra, P.
Show abstract
Natural Killer (NK) cells contribute to early immunity against Plasmodium falciparum by 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 (PfGBP-130) as a surface-expressed ligand on iRBCs that binds the I-domain of LFA-1 (LFA-1 I). Using an LFA-1 I-Fc fusion protein, we demonstrate stage-specific binding to iRBCs, and LC-MS/MS analysis of immunopreciptates of I-Fc bound to iRBC revealed PfGBP-130 as a high-confidence interactor. Recombinant PfGBP-130 binds NK and THP-1 cells in an LFA-1-dependent manner. Co-culture assays show that PfGBP-130 promotes NK cell activation, degranulation, and facilitates contact-dependent killing of iRBCs. Neutralizing antibodies against PfGBP-130 significantly impair these responses. Our findings establish PfGBP-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.
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