Work

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

Year: 2026

Type: article

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 ( Pf 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 immunopreciptates of αI-Fc bound to iRBC revealed Pf GBP-130 as a high-confidence interactor. Recombinant Pf GBP-130 binds NK and THP-1 cells in an LFA-1-dependent manner. Co-culture assays show that Pf GBP-130 promotes NK cell activation, degranulation, and facilitates contact-dependent killing of iRBCs. Neutralizing antibodies against Pf GBP-130 significantly impair these responses. Our findings establish Pf GBP-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.

Source: eLife

DOI: 10.7554/elife.110942.3