Author | Carvalho, Augusto M | |
Author | Bacellar, Olívia | |
Author | Carvalho, Edgar M | |
Access date | 2022-09-23T19:25:06Z | |
Available date | 2022-09-23T19:25:06Z | |
Document date | 2022 | |
Citation | CARVALHO, Augusto M; BACELLAR, Olívia; CARVALHO, Edgar M. Protection and Pathology in Leishmania braziliensis Infection. Pathogens, v. 11, n. 4, p. 1-11, 2022. | en_US |
ISSN | 2076-0817 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/54866 | |
Sponsorship | Institutos Nacionais de Saúde.
Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB).
Conselho Brasileiro de Desenvolvimento Científico e Tecnológico (CNPq). | en_US |
Language | eng | en_US |
Publisher | MDPI | en_US |
Rights | open access | en_US |
MeSH | Leishmaniasis | en_US |
MeSH | Leishmania braziliensis | en_US |
MeSH | Parasitic Diseases | en_US |
MeSH | Pathology | en_US |
Subject in Portuguese | Leishmaniose | en_US |
Subject in Portuguese | Leishmania braziliensis | en_US |
Subject in Portuguese | Infecção parasitária | en_US |
Subject in Portuguese | Patologia | en_US |
Subject in Portuguese | American tegumentary leishmaniasis | en_US |
Title | Protection and pathology in leishmania braziliensis infection | en_US |
Type | Article | en_US |
DOI | 10.3390/pathogens11040466 | |
Abstract | Leishmania killing is mediated by IFN-γ-activated macrophages, but IFN-γ production and macrophage activation are insufficient to control L. braziliensis infection. In American tegumentary leishmaniasis (ATL), pathology results from an exaggerated inflammatory response. This report presents an overview of our contributions regarding ATL pathogenesis, highlighting future directions to improve the management of L. braziliensis infection. Monocytes and lymphocytes from individuals exposed to L. braziliensis but who do not develop CL, i.e., subclinical infection (SC), exhibit lower respiratory burst and IFN-γ production, yet more efficiently kill L. braziliensis. As vaccines aimed at inducing IL-12 and IFN-γ do not sufficiently prevent CL, the elucidation of how subjects with SC infection kill Leishmania may lead to new approaches to controlling ATL. While inflammation arising from the recruitment of inflammatory cells via chemokines induced by IFN-γ and TNF or IL-17 is observed and contributes to pathology, cytotoxic CD8+ T cells and NK cells play a key role in the pathogenesis of L. braziliensis infection. The increased transcription of genes related to inflammation and cytotoxicity, e.g., granzyme A, granzyme B, NLRP3 and IL-1β, has been documented in CL tissue samples. The release of products by killed cells leads to NLRP3 inflammasome activation, IL-1β production and additional damage to skin and mucosal tissues. The use of drugs that downmodulate the inflammatory response in combination with chemotherapy improves the ATL cure rate and decreases healing time. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. 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. Conselho Nacional de Desenvolvimento Científico e Tecnológico. Salvador, BA, Brasil | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil / Universidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. 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. Conselho Nacional de Desenvolvimento Científico e Tecnológico. Salvador, BA, Brasil. | en_US |
Subject | Leishmaniasis | en_US |
Subject | Leishmania braziliensis | en_US |
Subject | Parasitic Diseases | en_US |
Subject | Pathology | en_US |
Subject | American tegumentary leishmaniasis | en_US |