Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis.
Adolescent
Adult
Aged
Antimony
Brazil
CD8-Positive T-Lymphocytes
/ immunology
Cytokines
/ metabolism
Female
Granzymes
Humans
Inflammation
Leishmania
/ immunology
Leishmania braziliensis
/ immunology
Leishmaniasis, Cutaneous
/ parasitology
Male
Matrix Metalloproteinase 9
Middle Aged
Necrosis
Skin
/ parasitology
Th1 Cells
/ immunology
Young Adult
Leishmania braziliensis
Leishmania skin test
cutaneous leishmaniasis
IFN-γ
IL-1β
TNF
Th1 immune response
inflammation
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
13 02 2021
13 02 2021
Historique:
received:
30
01
2020
accepted:
01
07
2020
pubmed:
4
7
2020
medline:
1
10
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). In CL patients LST is usually positive but a small percentage have negative LST. The aim of this study was to determine the clinical and immunologic features and response to antimony therapy in LST-negative CL patients. We compare the clinical presentation, response to therapy, and immune response of CL patients with negative vs positive LST. The clinical presentation was similar in both groups but LST-negative patients had a lower cure rate. In the lesions, LST-negative patients displayed less inflammation and necrosis, and higher frequency of CD8+ T cells. Mononuclear cells from LST-negative patients had a poor T helper 1 cell (Th1) response but levels of interleukin-1β (IL-1β), IL-6, IL-17, granzyme B, and metalloproteinase-9 (MMP-9) were similar to the LST-positive group upon stimulation with LA. Leishmania internalization and killing by macrophages were similar in both groups. Cure of disease was associated with restoration of Th1 response. In LST-negative patients, impaired Th1 response is associated with therapeutic failure. Increased frequency of CD8+ T cells and high production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology.
Sections du résumé
BACKGROUND
Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). In CL patients LST is usually positive but a small percentage have negative LST. The aim of this study was to determine the clinical and immunologic features and response to antimony therapy in LST-negative CL patients.
METHODS
We compare the clinical presentation, response to therapy, and immune response of CL patients with negative vs positive LST.
RESULTS
The clinical presentation was similar in both groups but LST-negative patients had a lower cure rate. In the lesions, LST-negative patients displayed less inflammation and necrosis, and higher frequency of CD8+ T cells. Mononuclear cells from LST-negative patients had a poor T helper 1 cell (Th1) response but levels of interleukin-1β (IL-1β), IL-6, IL-17, granzyme B, and metalloproteinase-9 (MMP-9) were similar to the LST-positive group upon stimulation with LA. Leishmania internalization and killing by macrophages were similar in both groups. Cure of disease was associated with restoration of Th1 response.
CONCLUSIONS
In LST-negative patients, impaired Th1 response is associated with therapeutic failure. Increased frequency of CD8+ T cells and high production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology.
Identifiants
pubmed: 32620011
pii: 5867185
doi: 10.1093/infdis/jiaa374
pmc: PMC7881333
doi:
Substances chimiques
Cytokines
0
Antimony
9IT35J3UV3
Granzymes
EC 3.4.21.-
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
527-535Subventions
Organisme : NIAID NIH HHS
ID : U01 AI136032
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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