ArticlePloS one2012
Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 91 citations in OpenAlex.
- Cytotoxic T Cell-Derived Granzyme B Is Increased in SevereFrontiers in immunology · 2019Trial
- Is the Association of Granzyme B and the Exported Parasite Hsp70 a Possible Trojan Horse of Severe Malaria?Advances in experimental medicine and biology · 2026Article
- Natural killer cell antibody-dependent cellular cytotoxicity toClinical & translational immunology · 2024Article
- Human granzyme B binds Plasmodium falciparum Hsp70-x and mediates antiplasmodial activity in vitro.Cell stress & chaperones · 2023Article
- Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells.International journal of molecular sciences · 2021Article
- Of membranes and malaria: phospholipid asymmetry in Plasmodium falciparum-infected red blood cells.Cellular and molecular life sciences : CMLS · 2021Review
- Role of Heat Shock Proteins in Immune Modulation in Malaria.Advances in experimental medicine and biology · 2021Article
- γδ T Cells KillJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion.International journal of molecular sciences · 2019Review
- Innate Lymphoid Cells in Protection, Pathology, and Adaptive Immunity During Apicomplexan Infection.Frontiers in immunology · 2019Review
- Gene expression of the liver of vaccination-protected mice in response to early patent infections of Plasmodium chabaudi blood-stage malaria.Malaria journal · 2018Article
- Poorly cytotoxic terminally differentiated CD56Blood advances · 2018Article
- Review
- Macromolecular Conjugate and Biological Carrier Approaches for the Targeted Delivery of Antibiotics.Antibiotics (Basel, Switzerland) · 2017Review
- Designing the Sniper: Improving Targeted Human Cytolytic Fusion Proteins for Anti-Cancer Therapy via Molecular Simulation.Biomedicines · 2017Review
- Article
- NK Cells: Uncertain Allies against Malaria.Frontiers in immunology · 2017Review
- Recombinant heat shock protein 70 functional peptide and alpha-fetoprotein epitope peptide vaccine elicits specific anti-tumor immunity.Oncotarget · 2016Article
- Oncolytic virotherapy for urological cancers.Nature reviews. Urology · 2016Review
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the early immune response to Plasmodium falciparum-infected erythrocytes (iRBC), Natural Killer (NK) cells are activated, which suggests an important role in innate anti-parasitic immunity. However, it is not well understood whether NK cells directly recognize iRBC or whether stimulation of NK cells depends mainly on activating signals from accessory cells through cell-to-cell contact or soluble factors. In the present study, we investigated the influence of membrane-bound host Heat shock protein (Hsp) 70 in triggering cytotoxicity of NK cells from malaria-naïve donors or the cell line NK92 against iRBC. Hsp70 and HLA-E membrane expression on iRBC and potential activatory NK cell receptors (NKG2C, CD94) were assessed by flow cytometry and immunoblot. Upon contact with iRBC, Granzyme B (GzmB) production and release was initiated by unstimulated and Hsp70-peptide (TKD) pre-stimulated NK cells, as determined by Western blot, RT-PCR and ELISPOT analysis. Eryptosis of iRBC was determined by Annexin V-staining. Our results suggest that presence of Hsp70 and absence of HLA-E on the membrane of iRBC prompt the infected host cells to become targets for NK cell-mediated cytotoxicity, as evidenced by impaired parasite development. Contact of iRBC with NK cells induced release of GzmB. We propose that following GzmB uptake, iRBC undergo eryptosis via a perforin-independent, GzmB-mediated mechanism. Since NK activity toward iRBC could be specifically enhanced by TKD peptide and abrogated to baseline levels by blocking Hsp70 exposure, we propose TKD as an innovative immunostimulatory agent to be tested as an adjunct to anti-parasitic treatments in vivo.
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