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Cited by 0Malaria Research and ControlImmune Cell Function and InteractionBlood groups and transfusion

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

Open access
Mukhtar, Osama, Dutt, Ravi, Panda, Ashutosh, Kumari, Poonam, Singh, Suneet Shekhar, Paul, Gourab, Prakash, Neha, Abbas, Madiha, Islam, Md Muzahidul, Arora, Priya, Tammour, Alma, Mohmmed, Asif, Kumar, Dhiraj, Malhotra, Pawan·2026·eLife
DOI 10.7554/elife.110942.3PMC PMC13218722

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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 immunoprecipitates 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 and 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.

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Research works printed but not linked: 35

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Metadata

Authors
Mukhtar, O., Dutt, R., Panda, A., Kumari, P., Singh, S. S., Paul, G., Prakash, N., Abbas, M., Islam, M. M., Arora, P., Tammour, A., Mohmmed, A., Kumar, D., & Malhotra, P.
Affiliations
International Centre for Genetic Engineering and Biotechnology (IN)
Corresponding author
Malhotra, Pawan
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2026-05-28
Volume
15
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.110942.3
PMC
PMC13218722
OpenAlex
W4413480300
Cited by
0
References
1
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • eLife (acceptedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Department of Science and Technology, Ministry of Science and Technology, India (BT/IC-06/003/91, DST/20/015)
  • Wellcome Trust/DBT India Alliance (IA/TSG/22/1/600422)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
Keywords
LFA-1, Plasmodium falciparum, infected erythrocytes, natural killer cells, NK cell activation, integrin ligands, I-domain, malaria immunity, parasite control, NK cell degranulation, host-directed therapy

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