Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature.
Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-γ within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-γ which triggers their ability to kill the intracellular parasites. Consistent with this, transcriptional a...
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ftdoajarticles:oai:doaj.org/article:831669485c7f4f5a89de9e4a4de5a7b9 2023-05-15T15:13:56+02:00 Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. Camila Farias Amorim Fernanda O Novais Ba T Nguyen Mauricio T Nascimento Jamile Lago Alexsandro S Lago Lucas P Carvalho Daniel P Beiting Phillip Scott 2021-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009321 https://doaj.org/article/831669485c7f4f5a89de9e4a4de5a7b9 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009321 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009321 https://doaj.org/article/831669485c7f4f5a89de9e4a4de5a7b9 PLoS Neglected Tropical Diseases, Vol 15, Iss 4, p e0009321 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009321 2022-12-31T14:48:54Z Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-γ within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-γ which triggers their ability to kill the intracellular parasites. Consistent with this, transcriptional analysis of patient lesions identified an interferon stimulated gene (ISG) signature. To determine whether localized L. braziliensis infection triggers a systemic immune response that may influence the disease, we performed RNA sequencing (RNA-seq) on the blood of L. braziliensis-infected patients and healthy controls. Functional enrichment analysis identified an ISG signature as the dominant transcriptional response in the blood of patients. This ISG signature was associated with an increase in monocyte- and macrophage-specific marker genes in the blood and elevated serum levels IFN-γ. A cytotoxicity signature, which is a dominant feature in the lesions, was also observed in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis-another localized infection-but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests a mechanism to limit systemic spread of the parasite, as well as enhance parasite control by pre-activating cells prior to lesion entry. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 4 e0009321 |
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 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Camila Farias Amorim Fernanda O Novais Ba T Nguyen Mauricio T Nascimento Jamile Lago Alexsandro S Lago Lucas P Carvalho Daniel P Beiting Phillip Scott Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-γ within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-γ which triggers their ability to kill the intracellular parasites. Consistent with this, transcriptional analysis of patient lesions identified an interferon stimulated gene (ISG) signature. To determine whether localized L. braziliensis infection triggers a systemic immune response that may influence the disease, we performed RNA sequencing (RNA-seq) on the blood of L. braziliensis-infected patients and healthy controls. Functional enrichment analysis identified an ISG signature as the dominant transcriptional response in the blood of patients. This ISG signature was associated with an increase in monocyte- and macrophage-specific marker genes in the blood and elevated serum levels IFN-γ. A cytotoxicity signature, which is a dominant feature in the lesions, was also observed in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis-another localized infection-but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests a mechanism to limit systemic spread of the parasite, as well as enhance parasite control by pre-activating cells prior to lesion entry. |
format |
Article in Journal/Newspaper |
author |
Camila Farias Amorim Fernanda O Novais Ba T Nguyen Mauricio T Nascimento Jamile Lago Alexsandro S Lago Lucas P Carvalho Daniel P Beiting Phillip Scott |
author_facet |
Camila Farias Amorim Fernanda O Novais Ba T Nguyen Mauricio T Nascimento Jamile Lago Alexsandro S Lago Lucas P Carvalho Daniel P Beiting Phillip Scott |
author_sort |
Camila Farias Amorim |
title |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. |
title_short |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. |
title_full |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. |
title_fullStr |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. |
title_full_unstemmed |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. |
title_sort |
localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic ifn-γ signature. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009321 https://doaj.org/article/831669485c7f4f5a89de9e4a4de5a7b9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 4, p e0009321 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009321 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009321 https://doaj.org/article/831669485c7f4f5a89de9e4a4de5a7b9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009321 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
4 |
container_start_page |
e0009321 |
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1766344438330687488 |