Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines.
The ability to reside and proliferate in macrophages is characteristic of several infectious agents that are of major importance to public health, including the intracellular parasites Trypanosoma cruzi (the etiological agent of Chagas disease) and Leishmania species (etiological agents of Kala-Azar...
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ftdoajarticles:oai:doaj.org/article:1c4dd807c45841baad0f43133553c53c 2023-05-15T15:13:10+02:00 Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. Shuyi Zhang Charles C Kim Sajeev Batra James H McKerrow P'ng Loke 2010-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000648 https://doaj.org/article/1c4dd807c45841baad0f43133553c53c EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2846935?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000648 https://doaj.org/article/1c4dd807c45841baad0f43133553c53c PLoS Neglected Tropical Diseases, Vol 4, Iss 3, p e648 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000648 2022-12-31T05:44:58Z The ability to reside and proliferate in macrophages is characteristic of several infectious agents that are of major importance to public health, including the intracellular parasites Trypanosoma cruzi (the etiological agent of Chagas disease) and Leishmania species (etiological agents of Kala-Azar and cutaneous leishmaniasis). Although recent studies have elucidated some of the ways macrophages respond to these pathogens, the relationships between activation programs elicited by these pathogens and the macrophage activation programs elicited by bacterial pathogens and cytokines have not been delineated.To provide a global perspective on the relationships between macrophage activation programs and to understand how certain pathogens circumvent them, we used transcriptional profiling by genome-wide microarray analysis to compare the responses of mouse macrophages following exposure to the intracellular parasites T. cruzi and Leishmania mexicana, the bacterial product lipopolysaccharide (LPS), and the cytokines IFNG, TNF, IFNB, IL-4, IL-10, and IL-17. We found that LPS induced a classical activation state that resembled macrophage stimulation by the Th1 cytokines IFNG and TNF. However, infection by the protozoan pathogen L. mexicana produced so few transcriptional changes that the infected macrophages were almost indistinguishable from uninfected cells. T. cruzi activated macrophages produced a transcriptional signature characterized by the induction of interferon-stimulated genes by 24 h post-infection. Despite this delayed IFN response by T. cruzi, the transcriptional response of macrophages infected by the kinetoplastid pathogens more closely resembled the transcriptional response of macrophages stimulated by the cytokines IL-4, IL-10, and IL-17 than macrophages stimulated by Th1 cytokines.This study provides global gene expression data for a diverse set of biologically significant pathogens and cytokines and identifies the relationships between macrophage activation states induced by these stimuli. By ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Azar ENVELOPE(-63.733,-63.733,-64.983,-64.983) PLoS Neglected Tropical Diseases 4 3 e648 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Shuyi Zhang Charles C Kim Sajeev Batra James H McKerrow P'ng Loke Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The ability to reside and proliferate in macrophages is characteristic of several infectious agents that are of major importance to public health, including the intracellular parasites Trypanosoma cruzi (the etiological agent of Chagas disease) and Leishmania species (etiological agents of Kala-Azar and cutaneous leishmaniasis). Although recent studies have elucidated some of the ways macrophages respond to these pathogens, the relationships between activation programs elicited by these pathogens and the macrophage activation programs elicited by bacterial pathogens and cytokines have not been delineated.To provide a global perspective on the relationships between macrophage activation programs and to understand how certain pathogens circumvent them, we used transcriptional profiling by genome-wide microarray analysis to compare the responses of mouse macrophages following exposure to the intracellular parasites T. cruzi and Leishmania mexicana, the bacterial product lipopolysaccharide (LPS), and the cytokines IFNG, TNF, IFNB, IL-4, IL-10, and IL-17. We found that LPS induced a classical activation state that resembled macrophage stimulation by the Th1 cytokines IFNG and TNF. However, infection by the protozoan pathogen L. mexicana produced so few transcriptional changes that the infected macrophages were almost indistinguishable from uninfected cells. T. cruzi activated macrophages produced a transcriptional signature characterized by the induction of interferon-stimulated genes by 24 h post-infection. Despite this delayed IFN response by T. cruzi, the transcriptional response of macrophages infected by the kinetoplastid pathogens more closely resembled the transcriptional response of macrophages stimulated by the cytokines IL-4, IL-10, and IL-17 than macrophages stimulated by Th1 cytokines.This study provides global gene expression data for a diverse set of biologically significant pathogens and cytokines and identifies the relationships between macrophage activation states induced by these stimuli. By ... |
format |
Article in Journal/Newspaper |
author |
Shuyi Zhang Charles C Kim Sajeev Batra James H McKerrow P'ng Loke |
author_facet |
Shuyi Zhang Charles C Kim Sajeev Batra James H McKerrow P'ng Loke |
author_sort |
Shuyi Zhang |
title |
Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
title_short |
Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
title_full |
Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
title_fullStr |
Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
title_full_unstemmed |
Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
title_sort |
delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000648 https://doaj.org/article/1c4dd807c45841baad0f43133553c53c |
long_lat |
ENVELOPE(-63.733,-63.733,-64.983,-64.983) |
geographic |
Arctic Azar |
geographic_facet |
Arctic Azar |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 3, p e648 (2010) |
op_relation |
http://europepmc.org/articles/PMC2846935?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000648 https://doaj.org/article/1c4dd807c45841baad0f43133553c53c |
op_doi |
https://doi.org/10.1371/journal.pntd.0000648 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
4 |
container_issue |
3 |
container_start_page |
e648 |
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1766343756212076544 |