Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.

<h4>Background</h4>The liver stages of malaria parasites are inhibited by cytokines such as interferon-γ or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen interme...

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Autores principales:	Nadya Depinay, Jean Francois Franetich, Anne Charlotte Grüner, Marjorie Mauduit, Jean-Marc Chavatte, Adrian J F Luty, Geert-Jan van Gemert, Robert W Sauerwein, Jean-Michel Siksik, Laurent Hannoun, Dominique Mazier, Georges Snounou, Laurent Rénia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18039d74296d45ac84cfab934fef6a55
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spelling	oai:doaj.org-article:18039d74296d45ac84cfab934fef6a552021-11-18T06:57:46ZInhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.1932-620310.1371/journal.pone.0017464https://doaj.org/article/18039d74296d45ac84cfab934fef6a552011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21394207/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The liver stages of malaria parasites are inhibited by cytokines such as interferon-γ or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-α possibly because of differences in the models used. We have reassessed the role of TNF-α in the different cellular systems used to study the Plasmodium pre-erythrocytic stages.<h4>Methods and findings</h4>Human or mouse TNF-α were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-α treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-α inhibition was mediated by a soluble factor present in the supernatant of TNF-α stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified.<h4>Conclusions</h4>Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection.Nadya DepinayJean Francois FranetichAnne Charlotte GrünerMarjorie MauduitJean-Marc ChavatteAdrian J F LutyGeert-Jan van GemertRobert W SauerweinJean-Michel SiksikLaurent HannounDominique MazierGeorges SnounouLaurent RéniaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17464 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadya Depinay Jean Francois Franetich Anne Charlotte Grüner Marjorie Mauduit Jean-Marc Chavatte Adrian J F Luty Geert-Jan van Gemert Robert W Sauerwein Jean-Michel Siksik Laurent Hannoun Dominique Mazier Georges Snounou Laurent Rénia Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
description	<h4>Background</h4>The liver stages of malaria parasites are inhibited by cytokines such as interferon-γ or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-α possibly because of differences in the models used. We have reassessed the role of TNF-α in the different cellular systems used to study the Plasmodium pre-erythrocytic stages.<h4>Methods and findings</h4>Human or mouse TNF-α were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-α treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-α inhibition was mediated by a soluble factor present in the supernatant of TNF-α stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified.<h4>Conclusions</h4>Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection.
format	article
author	Nadya Depinay Jean Francois Franetich Anne Charlotte Grüner Marjorie Mauduit Jean-Marc Chavatte Adrian J F Luty Geert-Jan van Gemert Robert W Sauerwein Jean-Michel Siksik Laurent Hannoun Dominique Mazier Georges Snounou Laurent Rénia
author_facet	Nadya Depinay Jean Francois Franetich Anne Charlotte Grüner Marjorie Mauduit Jean-Marc Chavatte Adrian J F Luty Geert-Jan van Gemert Robert W Sauerwein Jean-Michel Siksik Laurent Hannoun Dominique Mazier Georges Snounou Laurent Rénia
author_sort	Nadya Depinay
title	Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
title_short	Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
title_full	Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
title_fullStr	Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
title_full_unstemmed	Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
title_sort	inhibitory effect of tnf-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/18039d74296d45ac84cfab934fef6a55
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Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.

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