Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi.
We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+) T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the abilit...
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ftdoajarticles:oai:doaj.org/article:aa4120137c434c91b93db131fa49a7fe 2023-05-15T15:17:09+02:00 Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. Aline Guilmot Julie Bosse Yves Carlier Carine Truyens 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002291 https://doaj.org/article/aa4120137c434c91b93db131fa49a7fe EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3688561?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002291 https://doaj.org/article/aa4120137c434c91b93db131fa49a7fe PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2291 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002291 2022-12-31T06:26:32Z We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+) T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56(bright) NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells), while CD56(dim) NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 6 e2291 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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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 Aline Guilmot Julie Bosse Yves Carlier Carine Truyens Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
We previously reported that foetuses congenitally infected with Trypanosoma cruzi, the agent of Chagas disease, mount an adult-like parasite-specific CD8(+) T-cell response, producing IFN-g, and present an altered NK cell phenotype, possibly reflecting a post-activation state supported by the ability of the parasite to trigger IFN-g synthesis by NK cells in vitro. We here extended our knowledge on NK cell activation by the parasite. We compared the ability of T. cruzi to activate cord blood and adult NK cells from healthy individuals. Twenty-four hours co-culture of cord blood mononuclear cells with T. cruzi trypomastigotes and IL-15 induced high accumulation of IFN-g transcripts and IFN-g release. TNF-a, but not IL-10, was also produced. This was associated with up-regulation of CD69 and CD54, and down-regulation of CD62L on NK cells. The CD56(bright) NK cell subset was the major IFN-g responding subset (up to 70% IFN-g-positive cells), while CD56(dim) NK cells produced IFN-g to a lesser extent. The response points to a synergy between parasites and IL-15. The neonatal response, observed in all newborns, remained however slightly inferior to that of adults. Activation of IL-15-sensitized cord blood NK cells by the parasite required contacts with live/intact parasites. In addition, it depended on the engagement of TLR-2 and 4 and involved IL-12 and cross-talk with monocytes but not with myeloid dendritic cells, as shown by the use of neutralizing antibodies and cell depletion. This work highlights the ability of T. cruzi to trigger a robust IFN-g response by IL-15-sensitized human neonatal NK cells and the important role of monocytes in it, which might perhaps partially compensate for the neonatal defects of DCs. It suggests that monocyte- and IL-12- dependent IFN-g release by NK cells is a potentially important innate immune response pathway allowing T. cruzi to favour a type 1 immune response in neonates. |
format |
Article in Journal/Newspaper |
author |
Aline Guilmot Julie Bosse Yves Carlier Carine Truyens |
author_facet |
Aline Guilmot Julie Bosse Yves Carlier Carine Truyens |
author_sort |
Aline Guilmot |
title |
Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. |
title_short |
Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. |
title_full |
Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. |
title_fullStr |
Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. |
title_full_unstemmed |
Monocytes play an IL-12-dependent crucial role in driving cord blood NK cells to produce IFN-g in response to Trypanosoma cruzi. |
title_sort |
monocytes play an il-12-dependent crucial role in driving cord blood nk cells to produce ifn-g in response to trypanosoma cruzi. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002291 https://doaj.org/article/aa4120137c434c91b93db131fa49a7fe |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2291 (2013) |
op_relation |
http://europepmc.org/articles/PMC3688561?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002291 https://doaj.org/article/aa4120137c434c91b93db131fa49a7fe |
op_doi |
https://doi.org/10.1371/journal.pntd.0002291 |
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PLoS Neglected Tropical Diseases |
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6 |
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e2291 |
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