Cargando…

Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi

Visceral leishmaniasis is a potentially fatal infectious disease caused by the protozoan parasite Leishmania infantum/chagasi in the New World, or by L. donovani or L. infantum/chagasi in the Old World. Infection leads to a variety of outcomes ranging from asymptomatic infection to active disease, c...

Descripción completa

Detalles Bibliográficos
Autores principales: Ettinger, Nicholas A., Wilson, Mary E.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427198/
https://www.ncbi.nlm.nih.gov/pubmed/18575603
http://dx.doi.org/10.1371/journal.pntd.0000252
_version_ 1782156330423812096
author Ettinger, Nicholas A.
Wilson, Mary E.
author_facet Ettinger, Nicholas A.
Wilson, Mary E.
author_sort Ettinger, Nicholas A.
collection PubMed
description Visceral leishmaniasis is a potentially fatal infectious disease caused by the protozoan parasite Leishmania infantum/chagasi in the New World, or by L. donovani or L. infantum/chagasi in the Old World. Infection leads to a variety of outcomes ranging from asymptomatic infection to active disease, characterized by fevers, cachexia, hepatosplenomegaly and suppressed immune responses. We reasoned that events occurring during the initial few hours when the parasite encounters cells of the innate and adaptive immune systems are likely to influence the eventual immune response that develops. Therefore, we performed gene expression analysis using Affymetrix U133Plus2 microarray chips to investigate a model of early infection with human monocyte-derived macrophages (MDMs) challenged with wild-type L. chagasi parasites, with or without subsequent co-culture with Leishmania-naïve, autologous T-cells. Microarray data generated from total RNA were analyzed with software from the Bioconductor Project and functional clustering and pathway analysis were performed with DAVID and Gene Set Enrichment Analysis (GSEA), respectively. Many transcripts were down-regulated by infection in cultures containing macrophages alone, and the pattern indicated a lack of a classically activated phenotype. By contrast, the addition of autologous Leishmania-naïve T cells to infected macrophages resulted in a pattern of gene expression including many markers of type 1 immune cytokine activation (IFN-γ, IL-6, IL-1α, IL-1β). There was simultaneous up-regulation of a few markers of immune modulation (IL-10 cytokine accumulation; TGF-β Signaling Pathway). We suggest that the initial encounter between L. chagasi and cells of the innate and adaptive immune system stimulates primarily type 1 immune cytokine responses, despite a lack of classical macrophage activation. This local microenvironment at the site of parasite inoculation may determine the initial course of immune T-cell development.
format Text
id pubmed-2427198
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-24271982008-06-25 Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi Ettinger, Nicholas A. Wilson, Mary E. PLoS Negl Trop Dis Research Article Visceral leishmaniasis is a potentially fatal infectious disease caused by the protozoan parasite Leishmania infantum/chagasi in the New World, or by L. donovani or L. infantum/chagasi in the Old World. Infection leads to a variety of outcomes ranging from asymptomatic infection to active disease, characterized by fevers, cachexia, hepatosplenomegaly and suppressed immune responses. We reasoned that events occurring during the initial few hours when the parasite encounters cells of the innate and adaptive immune systems are likely to influence the eventual immune response that develops. Therefore, we performed gene expression analysis using Affymetrix U133Plus2 microarray chips to investigate a model of early infection with human monocyte-derived macrophages (MDMs) challenged with wild-type L. chagasi parasites, with or without subsequent co-culture with Leishmania-naïve, autologous T-cells. Microarray data generated from total RNA were analyzed with software from the Bioconductor Project and functional clustering and pathway analysis were performed with DAVID and Gene Set Enrichment Analysis (GSEA), respectively. Many transcripts were down-regulated by infection in cultures containing macrophages alone, and the pattern indicated a lack of a classically activated phenotype. By contrast, the addition of autologous Leishmania-naïve T cells to infected macrophages resulted in a pattern of gene expression including many markers of type 1 immune cytokine activation (IFN-γ, IL-6, IL-1α, IL-1β). There was simultaneous up-regulation of a few markers of immune modulation (IL-10 cytokine accumulation; TGF-β Signaling Pathway). We suggest that the initial encounter between L. chagasi and cells of the innate and adaptive immune system stimulates primarily type 1 immune cytokine responses, despite a lack of classical macrophage activation. This local microenvironment at the site of parasite inoculation may determine the initial course of immune T-cell development. Public Library of Science 2008-06-25 /pmc/articles/PMC2427198/ /pubmed/18575603 http://dx.doi.org/10.1371/journal.pntd.0000252 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Ettinger, Nicholas A.
Wilson, Mary E.
Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi
title Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi
title_full Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi
title_fullStr Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi
title_full_unstemmed Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi
title_short Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi
title_sort macrophage and t-cell gene expression in a model of early infection with the protozoan leishmania chagasi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427198/
https://www.ncbi.nlm.nih.gov/pubmed/18575603
http://dx.doi.org/10.1371/journal.pntd.0000252
work_keys_str_mv AT ettingernicholasa macrophageandtcellgeneexpressioninamodelofearlyinfectionwiththeprotozoanleishmaniachagasi
AT wilsonmarye macrophageandtcellgeneexpressioninamodelofearlyinfectionwiththeprotozoanleishmaniachagasi