Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.

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 ce...

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Autores principales:	Evelyn Böttger, Gabriele Multhoff, Jürgen F J Kun, Meral Esen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6efbceb987d4ce2ac84d91b46d0616b
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spelling	oai:doaj.org-article:d6efbceb987d4ce2ac84d91b46d0616b2021-11-18T07:25:03ZPlasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.1932-620310.1371/journal.pone.0033774https://doaj.org/article/d6efbceb987d4ce2ac84d91b46d0616b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22438997/?tool=EBIhttps://doaj.org/toc/1932-6203In 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.Evelyn BöttgerGabriele MulthoffJürgen F J KunMeral EsenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33774 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Evelyn Böttger Gabriele Multhoff Jürgen F J Kun Meral Esen Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
description	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.
format	article
author	Evelyn Böttger Gabriele Multhoff Jürgen F J Kun Meral Esen
author_facet	Evelyn Böttger Gabriele Multhoff Jürgen F J Kun Meral Esen
author_sort	Evelyn Böttger
title	Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
title_short	Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
title_full	Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
title_fullStr	Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
title_full_unstemmed	Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.
title_sort	plasmodium falciparum-infected erythrocytes induce granzyme b by nk cells through expression of host-hsp70.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d6efbceb987d4ce2ac84d91b46d0616b
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_version_	1718423501882261504

Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70.

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