Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.

Infection of macrophages by the intracellular protozoan Leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. The underlying molecular mechanisms involved remain largely unknown. In this study, we assessed ep...

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Autores principales:	Alexandra K Marr, Julia L MacIsaac, Ruiwei Jiang, Adriana M Airo, Michael S Kobor, W Robert McMaster
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ee44871f10d64f0ebcca5ebacb35e1bb
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spelling	oai:doaj.org-article:ee44871f10d64f0ebcca5ebacb35e1bb2021-11-25T05:45:57ZLeishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.1553-73661553-737410.1371/journal.ppat.1004419https://doaj.org/article/ee44871f10d64f0ebcca5ebacb35e1bb2014-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1004419https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Infection of macrophages by the intracellular protozoan Leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. The underlying molecular mechanisms involved remain largely unknown. In this study, we assessed epigenetic changes in macrophage DNA methylation in response to infection with L. donovani as a possible mechanism for Leishmania driven deactivation of host defense. We quantified and detected genome-wide changes of cytosine methylation status in the macrophage genome resulting from L. donovani infection. A high confidence set of 443 CpG sites was identified with changes in methylation that correlated with live L. donovani infection. These epigenetic changes affected genes that play a critical role in host defense such as the JAK/STAT signaling pathway and the MAPK signaling pathway. These results provide strong support for a new paradigm in host-pathogen responses, where upon infection the pathogen induces epigenetic changes in the host cell genome resulting in downregulation of innate immunity thereby enabling pathogen survival and replication. We therefore propose a model whereby Leishmania induced epigenetic changes result in permanent down regulation of host defense mechanisms to protect intracellular replication and survival of parasitic cells.Alexandra K MarrJulia L MacIsaacRuiwei JiangAdriana M AiroMichael S KoborW Robert McMasterPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 10, p e1004419 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Alexandra K Marr Julia L MacIsaac Ruiwei Jiang Adriana M Airo Michael S Kobor W Robert McMaster Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
description	Infection of macrophages by the intracellular protozoan Leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. The underlying molecular mechanisms involved remain largely unknown. In this study, we assessed epigenetic changes in macrophage DNA methylation in response to infection with L. donovani as a possible mechanism for Leishmania driven deactivation of host defense. We quantified and detected genome-wide changes of cytosine methylation status in the macrophage genome resulting from L. donovani infection. A high confidence set of 443 CpG sites was identified with changes in methylation that correlated with live L. donovani infection. These epigenetic changes affected genes that play a critical role in host defense such as the JAK/STAT signaling pathway and the MAPK signaling pathway. These results provide strong support for a new paradigm in host-pathogen responses, where upon infection the pathogen induces epigenetic changes in the host cell genome resulting in downregulation of innate immunity thereby enabling pathogen survival and replication. We therefore propose a model whereby Leishmania induced epigenetic changes result in permanent down regulation of host defense mechanisms to protect intracellular replication and survival of parasitic cells.
format	article
author	Alexandra K Marr Julia L MacIsaac Ruiwei Jiang Adriana M Airo Michael S Kobor W Robert McMaster
author_facet	Alexandra K Marr Julia L MacIsaac Ruiwei Jiang Adriana M Airo Michael S Kobor W Robert McMaster
author_sort	Alexandra K Marr
title	Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
title_short	Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
title_full	Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
title_fullStr	Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
title_full_unstemmed	Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.
title_sort	leishmania donovani infection causes distinct epigenetic dna methylation changes in host macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ee44871f10d64f0ebcca5ebacb35e1bb
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Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages.

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