NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis.
Cutaneous leishmaniasis exhibits a spectrum of clinical presentations dependent upon the parasites' persistence and host immunopathologic responses. Although cytolytic CD8 T cells cannot control the parasites, they significantly contribute to pathologic responses. In a murine model of cutaneous...
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ftdoajarticles:oai:doaj.org/article:e0207c6016624022a4aa50a9a9f1c4c6 2023-10-09T21:49:06+02:00 NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. Laís A Sacramento Camila Farias Amorim Taís M Campos Maíra Saldanha Sérgio Arruda Lucas P Carvalho Daniel P Beiting Edgar M Carvalho Fernanda O Novais Phillip Scott 2023-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011552 https://doaj.org/article/e0207c6016624022a4aa50a9a9f1c4c6 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011552 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011552 https://doaj.org/article/e0207c6016624022a4aa50a9a9f1c4c6 PLoS Neglected Tropical Diseases, Vol 17, Iss 8, p e0011552 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011552 2023-09-10T00:37:58Z Cutaneous leishmaniasis exhibits a spectrum of clinical presentations dependent upon the parasites' persistence and host immunopathologic responses. Although cytolytic CD8 T cells cannot control the parasites, they significantly contribute to pathologic responses. In a murine model of cutaneous leishmaniasis, we previously found that NKG2D plays a role in the ability of cytolytic CD8 T cells to promote disease in leishmanial lesions. Here, we investigated whether NKG2D plays a role in human disease. We found that NKG2D and its ligands were expressed within lesions from L. braziliensis-infected patients and that IL-15 and IL-1β were factors driving NKG2D and NKG2D ligand expression, respectively. Blocking NKG2D reduced degranulation by CD8 T cells in a subset of patients. Additionally, our transcriptional analysis of patients' lesions found that patients who failed the first round of treatment exhibited higher expression of KLRK1, the gene coding for NKG2D, than those who responded to treatment. These findings suggest that NKG2D may be a promising therapeutic target for ameliorating disease severity in cutaneous leishmaniasis caused by L. braziliensis infection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 8 e0011552 |
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 Laís A Sacramento Camila Farias Amorim Taís M Campos Maíra Saldanha Sérgio Arruda Lucas P Carvalho Daniel P Beiting Edgar M Carvalho Fernanda O Novais Phillip Scott NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Cutaneous leishmaniasis exhibits a spectrum of clinical presentations dependent upon the parasites' persistence and host immunopathologic responses. Although cytolytic CD8 T cells cannot control the parasites, they significantly contribute to pathologic responses. In a murine model of cutaneous leishmaniasis, we previously found that NKG2D plays a role in the ability of cytolytic CD8 T cells to promote disease in leishmanial lesions. Here, we investigated whether NKG2D plays a role in human disease. We found that NKG2D and its ligands were expressed within lesions from L. braziliensis-infected patients and that IL-15 and IL-1β were factors driving NKG2D and NKG2D ligand expression, respectively. Blocking NKG2D reduced degranulation by CD8 T cells in a subset of patients. Additionally, our transcriptional analysis of patients' lesions found that patients who failed the first round of treatment exhibited higher expression of KLRK1, the gene coding for NKG2D, than those who responded to treatment. These findings suggest that NKG2D may be a promising therapeutic target for ameliorating disease severity in cutaneous leishmaniasis caused by L. braziliensis infection. |
format |
Article in Journal/Newspaper |
author |
Laís A Sacramento Camila Farias Amorim Taís M Campos Maíra Saldanha Sérgio Arruda Lucas P Carvalho Daniel P Beiting Edgar M Carvalho Fernanda O Novais Phillip Scott |
author_facet |
Laís A Sacramento Camila Farias Amorim Taís M Campos Maíra Saldanha Sérgio Arruda Lucas P Carvalho Daniel P Beiting Edgar M Carvalho Fernanda O Novais Phillip Scott |
author_sort |
Laís A Sacramento |
title |
NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
title_short |
NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
title_full |
NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
title_fullStr |
NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
title_full_unstemmed |
NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
title_sort |
nkg2d promotes cd8 t cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011552 https://doaj.org/article/e0207c6016624022a4aa50a9a9f1c4c6 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 8, p e0011552 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011552 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011552 https://doaj.org/article/e0207c6016624022a4aa50a9a9f1c4c6 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011552 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
8 |
container_start_page |
e0011552 |
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1779312126376017920 |