Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/36107
Title: Pro-cellular exhaustion markers are associated with splenic microarchitecture disorganization and parasite load in dogs with visceral leishmaniasis
Authors: Souza, Tainã Luís de
Silva, Aurea Virginia Andrade da
Pereira, Luiza de Oliveira Ramos
Figueiredo, Fabiano Borges
Mendes Junior, Artur Augusto Velho
Menezes, Rodrigo Caldas
Mendes-da-Cruz, Daniella Areas
Boité, Mariana Côrtes
Cupolillo, Elisa
Porrozzi, Renato
Morgado, Fernanda Nazaré
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Paraná, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas Sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
Abstract: In canine visceral leishmaniasis (CVL), splenic white pulp (SWP) disorganization has been associated with disease progression, reduced cytokine and chemokine expression and failure to control the parasite load. This profile is compatible with the cellular exhaustion previously shown in human visceral leishmaniasis. The present study aimed to evaluate the in situ expression of cellular exhaustion markers and their relation to clinical signs, SWP disorganization and parasite load. Forty dogs naturally infected by Leishmania infantum were grouped according to levels of SWP organization and parasite load. SWP disorganization was associated with reductions in the periarteriolar lymphatic sheath and lymphoid follicles/mm2 and worsening of the disease. Apoptotic cells expressing CTLA-4+ increased in dogs with disorganized SWP and a high parasite load. In the same group, PD-L1 and LAG-3 gene expression were reduced. A higher number of CD21+TIM-3+ B cells was detected in disorganized spleens than in organized spleens. Apoptosis is involved in periarteriolar lymphatic sheath reduction and lymphoid follicle atrophy and is associated with CTLA-4+ cell reductions in the splenic tissue of dogs with visceral leishmaniasis (VL). Failure to control the parasite load was observed, suggesting that cell exhaustion followed by T and B cell apoptosis plays a role in the immunosuppression observed in CVL.
Keywords: Canine visceral leishmaniasis
Leishmania infantum
Dogs
Splenic white pulp
Issue Date: 2019
Publisher: 0028-0836
Citation: SOUZA, Tainã Luís de et al. Pro-cellular exhaustion markers are associated with splenic microarchitecture disorganization and parasite load in dogs with visceral leishmaniasis. Nature, v. 9, p. 1-14, 2019.
DOI: 10.1038/s41598-019-49344-1
ISSN: 0028-0836
Copyright: restricted access
Appears in Collections:PR - ICC - Artigos de Periódicos
IOC - Artigos de Periódicos
INI - Artigos de Periódicos

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