Leishmania donovani Infection Causes Distinct Epigenetic DNA Methylation Changes in Host Macrophages

Alexandra K. Marr, Julia L. MacIsaac, Ruiwei Jiang, Adriana M. Airo, Michael S. Kobor, W. Robert McMaster

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalPLoS Pathogens
Volume10
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014
Externally publishedYes

Fingerprint

Leishmania donovani
DNA Methylation
Epigenomics
Macrophages
Leishmania
Infection
Down-Regulation
Genome
Methylation
Cytosine
Innate Immunity
Cell Survival
Parasites
Genes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Leishmania donovani Infection Causes Distinct Epigenetic DNA Methylation Changes in Host Macrophages. / Marr, Alexandra K.; MacIsaac, Julia L.; Jiang, Ruiwei; Airo, Adriana M.; Kobor, Michael S.; McMaster, W. Robert.

In: PLoS Pathogens, Vol. 10, No. 10, 01.10.2014.

Research output: Contribution to journalArticle

Marr, Alexandra K. ; MacIsaac, Julia L. ; Jiang, Ruiwei ; Airo, Adriana M. ; Kobor, Michael S. ; McMaster, W. Robert. / Leishmania donovani Infection Causes Distinct Epigenetic DNA Methylation Changes in Host Macrophages. In: PLoS Pathogens. 2014 ; Vol. 10, No. 10.
@article{773180c2ddbd4b599361bfcd6a3d9f32,
title = "Leishmania donovani Infection Causes Distinct Epigenetic DNA Methylation Changes in Host Macrophages",
abstract = "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.",
author = "Marr, {Alexandra K.} and MacIsaac, {Julia L.} and Ruiwei Jiang and Airo, {Adriana M.} and Kobor, {Michael S.} and McMaster, {W. Robert}",
year = "2014",
month = "10",
day = "1",
doi = "10.1371/journal.ppat.1004419",
language = "English",
volume = "10",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Leishmania donovani Infection Causes Distinct Epigenetic DNA Methylation Changes in Host Macrophages

AU - Marr, Alexandra K.

AU - MacIsaac, Julia L.

AU - Jiang, Ruiwei

AU - Airo, Adriana M.

AU - Kobor, Michael S.

AU - McMaster, W. Robert

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908321127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908321127&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1004419

DO - 10.1371/journal.ppat.1004419

M3 - Article

VL - 10

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 10

ER -