Regulation of global gene expression in human Loa loa infection is a function of chronicity.
Human filarial infection is characterized by downregulated parasite-antigen specific T cell responses but distinct differences exist between patients with longstanding infection (endemics) and those who acquired infection through temporary residency or visits to filarial-endemic regions (expatriates...
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ftdoajarticles:oai:doaj.org/article:40ed9cae3bbc4da3a364825840a17a11 2023-05-15T15:12:25+02:00 Regulation of global gene expression in human Loa loa infection is a function of chronicity. Cathy Steel Sudhir Varma Thomas B Nutman 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001527 https://doaj.org/article/40ed9cae3bbc4da3a364825840a17a11 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3289604?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001527 https://doaj.org/article/40ed9cae3bbc4da3a364825840a17a11 PLoS Neglected Tropical Diseases, Vol 6, Iss 2, p e1527 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001527 2023-01-08T01:27:15Z Human filarial infection is characterized by downregulated parasite-antigen specific T cell responses but distinct differences exist between patients with longstanding infection (endemics) and those who acquired infection through temporary residency or visits to filarial-endemic regions (expatriates).To characterize mechanisms underlying differences in T cells, analysis of global gene expression using human spotted microarrays was conducted on CD4(+) and CD8(+) T cells from microfilaremic Loa loa-infected endemic and expatriate patients. Assessment of unstimulated cells showed overexpression of genes linked to inflammation and caspase-associated cell death, particularly in endemics, and enrichment of the Th1/Th2 canonical pathway in endemic CD4(+) cells. However, pathways within CD8(+) unstimulated cells were most significantly enriched in both patient groups. Antigen (Ag)-driven gene expression was assessed to microfilarial Ag (MfAg) and to the nonparasite Ag streptolysin O (SLO). For MfAg-driven cells, the number of genes differing significantly from unstimulated cells was greater in endemics compared to expatriates (p<0.0001). Functional analysis showed a differential increase in genes associated with NFkB (both groups) and caspase activation (endemics). While the expatriate response to MfAg was primarily a CD4(+) pro-inflammatory one, the endemic response included CD4(+) and CD8(+) cells and was linked to insulin signaling, histone complexes, and ubiquitination. Unlike the enrichment of canonical pathways in CD8(+) unstimulated cells, both groups showed pathway enrichment in CD4(+) cells to MfAg. Contrasting with the divergent responses to MfAg seen between endemics and expatriates, the CD4(+) response to SLO was similar; however, CD8(+) cells differed strongly in the nature and numbers (156 [endemics] vs 36 [expatriates]) of genes with differential expression.These data suggest several important pathways are responsible for the different outcomes seen among filarial-infected patients with varying levels ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 2 e1527 |
institution |
Open Polar |
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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 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Cathy Steel Sudhir Varma Thomas B Nutman Regulation of global gene expression in human Loa loa infection is a function of chronicity. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Human filarial infection is characterized by downregulated parasite-antigen specific T cell responses but distinct differences exist between patients with longstanding infection (endemics) and those who acquired infection through temporary residency or visits to filarial-endemic regions (expatriates).To characterize mechanisms underlying differences in T cells, analysis of global gene expression using human spotted microarrays was conducted on CD4(+) and CD8(+) T cells from microfilaremic Loa loa-infected endemic and expatriate patients. Assessment of unstimulated cells showed overexpression of genes linked to inflammation and caspase-associated cell death, particularly in endemics, and enrichment of the Th1/Th2 canonical pathway in endemic CD4(+) cells. However, pathways within CD8(+) unstimulated cells were most significantly enriched in both patient groups. Antigen (Ag)-driven gene expression was assessed to microfilarial Ag (MfAg) and to the nonparasite Ag streptolysin O (SLO). For MfAg-driven cells, the number of genes differing significantly from unstimulated cells was greater in endemics compared to expatriates (p<0.0001). Functional analysis showed a differential increase in genes associated with NFkB (both groups) and caspase activation (endemics). While the expatriate response to MfAg was primarily a CD4(+) pro-inflammatory one, the endemic response included CD4(+) and CD8(+) cells and was linked to insulin signaling, histone complexes, and ubiquitination. Unlike the enrichment of canonical pathways in CD8(+) unstimulated cells, both groups showed pathway enrichment in CD4(+) cells to MfAg. Contrasting with the divergent responses to MfAg seen between endemics and expatriates, the CD4(+) response to SLO was similar; however, CD8(+) cells differed strongly in the nature and numbers (156 [endemics] vs 36 [expatriates]) of genes with differential expression.These data suggest several important pathways are responsible for the different outcomes seen among filarial-infected patients with varying levels ... |
format |
Article in Journal/Newspaper |
author |
Cathy Steel Sudhir Varma Thomas B Nutman |
author_facet |
Cathy Steel Sudhir Varma Thomas B Nutman |
author_sort |
Cathy Steel |
title |
Regulation of global gene expression in human Loa loa infection is a function of chronicity. |
title_short |
Regulation of global gene expression in human Loa loa infection is a function of chronicity. |
title_full |
Regulation of global gene expression in human Loa loa infection is a function of chronicity. |
title_fullStr |
Regulation of global gene expression in human Loa loa infection is a function of chronicity. |
title_full_unstemmed |
Regulation of global gene expression in human Loa loa infection is a function of chronicity. |
title_sort |
regulation of global gene expression in human loa loa infection is a function of chronicity. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001527 https://doaj.org/article/40ed9cae3bbc4da3a364825840a17a11 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 2, p e1527 (2012) |
op_relation |
http://europepmc.org/articles/PMC3289604?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001527 https://doaj.org/article/40ed9cae3bbc4da3a364825840a17a11 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001527 |
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PLoS Neglected Tropical Diseases |
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6 |
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2 |
container_start_page |
e1527 |
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