Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria

Interleukin (IL)-10, a non-redundant anti-inflammatory cytokine is produced by different cells and its production involves activation of cell-specific transcriptional regulatory machinery in response to specific pathogen. We have previously demonstrated downregulated levels of IL-10 in severe falcip...

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Main Authors:	Mahanta, Anusree, Baruah, Shashi
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673438/

id	pubmed-4673438
recordtype	oai_dc
spelling	pubmed-46734382015-12-17 Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria Mahanta, Anusree Baruah, Shashi Original Article Interleukin (IL)-10, a non-redundant anti-inflammatory cytokine is produced by different cells and its production involves activation of cell-specific transcriptional regulatory machinery in response to specific pathogen. We have previously demonstrated downregulated levels of IL-10 in severe falciparum malaria. The present study investigated transcriptional regulation of IL-10 in severe malaria. Comparative expression analysis of cell-specific signalling proteins and transcription factors for IL-10 production during the stage of active infection and with resolution of parasitaemia was performed. Interestingly, T-bet and GATA3, the Th1 and Th2 transcription factors, respectively, were downregulated in severe malaria with fold change values of 0.59 and 0.86. Increase in the levels of both the factors with resolution of parasitaemia implicated a role for parasite in depressed levels of these factors. Further support for probable parasite manipulation of GATA3 was obtained from negative correlation of GATA3 with parasitaemia. In addition, a role for interferon-α in suppressing IL-10 transcription was evident from its negative correlation with GATA3 and IL-10 levels. In summary, IL-10 transcription in Th1 and Th2 is defective and appears to have major contribution to low levels in severe malaria. Nature Publishing Group 2015-11-06 /pmc/articles/PMC4673438/ /pubmed/26682056 http://dx.doi.org/10.1038/cti.2015.30 Text en Copyright © 2015 Australasian Society for Immunology Inc. http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mahanta, Anusree Baruah, Shashi
spellingShingle	Mahanta, Anusree Baruah, Shashi Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria
author_facet	Mahanta, Anusree Baruah, Shashi
author_sort	Mahanta, Anusree
title	Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria
title_short	Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria
title_full	Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria
title_fullStr	Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria
title_full_unstemmed	Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria
title_sort	lower expression of gata3 and t-bet correlates with downregulated il-10 in severe falciparum malaria
description	Interleukin (IL)-10, a non-redundant anti-inflammatory cytokine is produced by different cells and its production involves activation of cell-specific transcriptional regulatory machinery in response to specific pathogen. We have previously demonstrated downregulated levels of IL-10 in severe falciparum malaria. The present study investigated transcriptional regulation of IL-10 in severe malaria. Comparative expression analysis of cell-specific signalling proteins and transcription factors for IL-10 production during the stage of active infection and with resolution of parasitaemia was performed. Interestingly, T-bet and GATA3, the Th1 and Th2 transcription factors, respectively, were downregulated in severe malaria with fold change values of 0.59 and 0.86. Increase in the levels of both the factors with resolution of parasitaemia implicated a role for parasite in depressed levels of these factors. Further support for probable parasite manipulation of GATA3 was obtained from negative correlation of GATA3 with parasitaemia. In addition, a role for interferon-α in suppressing IL-10 transcription was evident from its negative correlation with GATA3 and IL-10 levels. In summary, IL-10 transcription in Th1 and Th2 is defective and appears to have major contribution to low levels in severe malaria.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673438/
_version_	1613510993555488768

Lower expression of GATA3 and T-bet correlates with downregulated IL-10 in severe falciparum malaria

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