Author | Carvalho, Augusto Marcelino Pedreira de | |
Author | Guimarães, Luiz H. | |
Author | Costa, Rúbia | |
Author | Saldanha, Maíra G. | |
Author | Prates, Iana | |
Author | Carvalho, Lucas Pedreira | |
Author | Arruda, Sérgio Marcos | |
Author | Carvalho Filho, Edgar Marcelino | |
Access date | 2020-08-11T13:11:48Z | |
Available date | 2020-08-11T13:11:48Z | |
Document date | 2020 | |
Citation | CARVALHO, Augusto Marcelino de Pedreira de et al. Impaired Th1 response is associated therapeutic failure in patients with cutaneous leishmaniasis caused by Leishmania braziliensis. The Journal of Infectious Diseases, p. 1-20, 2020. | pt_BR |
ISSN | 0022-1899 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/42651 | |
Sponsorship | National Institutes of Health (grant number AI 136032). | pt_BR |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Leishmaniose cutânea | pt_BR |
Subject in Portuguese | Leishmania braziliensis | pt_BR |
Subject in Portuguese | Testes cutâneos | pt_BR |
Subject in Portuguese | Resposta imune | pt_BR |
Subject in Portuguese | Inflamação | pt_BR |
Title | Impaired Th1 response is associated therapeutic failure in patients with cutaneous leishmaniasis caused by Leishmania braziliensis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1093/infdis/jiaa374 | |
Abstract | Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). CL patients usually present a positive LST, but as small percentage have a negative LST (LST-). The aim of this study was to determine the clinic and immunologic features and response to antimony therapy in LST- 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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal do Sul da Bahia. Teixeira de Freitas, BA, Brazil. | pt_BR |
Affilliation | Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil. | pt_BR |
Subject | Cutaneous leishmaniasis | pt_BR |
Subject | Leishmania braziliensis | pt_BR |
Subject | Leishmania skin test | pt_BR |
Subject | IFN-γ | pt_BR |
Subject | TNF | pt_BR |
Subject | Th1 immune response | pt_BR |
Subject | Inflamação | pt_BR |
Subject | IL-1β | pt_BR |