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Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis

BACKGROUND: Leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania protozoa that are transmitted to mammalian hosts by infected sand flies. Infection is associated with distinct clinical manifestations that include cutaneous, mucocutaneous and visceral lesions. Visceral leis...

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Autores principales: Nico, Dirlei, Maran, Naiara, Santos, Leonardo, Ramos-Junior, Erivan Schnaider, Mantuano, Natália Rodrigues, Coutinho, Joseane Lima Prado, Vale, Andre Macedo, Freire-de-Lima, Celio Geraldo, Todeschini, Adriane, Rodrigues, Juliany Cola Fernandes, Palatnik-de-Sousa, Clarisa Beatriz, Morrot, Alexandre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340829/
https://www.ncbi.nlm.nih.gov/pubmed/25874567
http://dx.doi.org/10.1186/s13071-015-0721-9
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author Nico, Dirlei
Maran, Naiara
Santos, Leonardo
Ramos-Junior, Erivan Schnaider
Mantuano, Natália Rodrigues
Coutinho, Joseane Lima Prado
Vale, Andre Macedo
Freire-de-Lima, Celio Geraldo
Todeschini, Adriane
Rodrigues, Juliany Cola Fernandes
Palatnik-de-Sousa, Clarisa Beatriz
Morrot, Alexandre
author_facet Nico, Dirlei
Maran, Naiara
Santos, Leonardo
Ramos-Junior, Erivan Schnaider
Mantuano, Natália Rodrigues
Coutinho, Joseane Lima Prado
Vale, Andre Macedo
Freire-de-Lima, Celio Geraldo
Todeschini, Adriane
Rodrigues, Juliany Cola Fernandes
Palatnik-de-Sousa, Clarisa Beatriz
Morrot, Alexandre
author_sort Nico, Dirlei
collection PubMed
description BACKGROUND: Leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania protozoa that are transmitted to mammalian hosts by infected sand flies. Infection is associated with distinct clinical manifestations that include cutaneous, mucocutaneous and visceral lesions. Visceral leishmaniasis (VL) is the most severe form of the disease and is considered second in terms of mortality and fourth in terms of morbidity among tropical diseases. IFN-γ-producing T cells are involved in protection against the disease. METHODS: CD43(+/+) and CD43(-/-) mice on a C57BL/6 background were intravenously injected with 5 × 10 (7) amastigotes of Leishmania (L.) infantum chagasi, and 30 days after infection the clinical signs of disease were examined; the splenocytes were isolated and assayed for cytokine production; and the livers were removed for phenotypic analysis of T cell subsets by flow cytometry. RESULTS: We report that mice lacking CD43 display increased susceptibility to infection by Leishmania (L.) infantum chagasi, with higher parasite burdens than wild-type mice. The increased susceptibility of CD43(−/−) mice were associated with a weakened delayed hypersensitivity response and reduced levels of IgG2a antibodies to leishmania antigens. We further showed that expression of CD43 defines a major intrahepatic CD4(+) and CD8(+) T cell subsets with pro-inflammatory phenotypes and leads to increased levels of IFN-γ secretion by activated splenocytes. CONCLUSIONS: Our findings point to a role of CD43 in the development of host resistance to visceral leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0721-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-43408292015-02-27 Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis Nico, Dirlei Maran, Naiara Santos, Leonardo Ramos-Junior, Erivan Schnaider Mantuano, Natália Rodrigues Coutinho, Joseane Lima Prado Vale, Andre Macedo Freire-de-Lima, Celio Geraldo Todeschini, Adriane Rodrigues, Juliany Cola Fernandes Palatnik-de-Sousa, Clarisa Beatriz Morrot, Alexandre Parasit Vectors Research BACKGROUND: Leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania protozoa that are transmitted to mammalian hosts by infected sand flies. Infection is associated with distinct clinical manifestations that include cutaneous, mucocutaneous and visceral lesions. Visceral leishmaniasis (VL) is the most severe form of the disease and is considered second in terms of mortality and fourth in terms of morbidity among tropical diseases. IFN-γ-producing T cells are involved in protection against the disease. METHODS: CD43(+/+) and CD43(-/-) mice on a C57BL/6 background were intravenously injected with 5 × 10 (7) amastigotes of Leishmania (L.) infantum chagasi, and 30 days after infection the clinical signs of disease were examined; the splenocytes were isolated and assayed for cytokine production; and the livers were removed for phenotypic analysis of T cell subsets by flow cytometry. RESULTS: We report that mice lacking CD43 display increased susceptibility to infection by Leishmania (L.) infantum chagasi, with higher parasite burdens than wild-type mice. The increased susceptibility of CD43(−/−) mice were associated with a weakened delayed hypersensitivity response and reduced levels of IgG2a antibodies to leishmania antigens. We further showed that expression of CD43 defines a major intrahepatic CD4(+) and CD8(+) T cell subsets with pro-inflammatory phenotypes and leads to increased levels of IFN-γ secretion by activated splenocytes. CONCLUSIONS: Our findings point to a role of CD43 in the development of host resistance to visceral leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0721-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-02-19 /pmc/articles/PMC4340829/ /pubmed/25874567 http://dx.doi.org/10.1186/s13071-015-0721-9 Text en © Nico et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Nico, Dirlei
Maran, Naiara
Santos, Leonardo
Ramos-Junior, Erivan Schnaider
Mantuano, Natália Rodrigues
Coutinho, Joseane Lima Prado
Vale, Andre Macedo
Freire-de-Lima, Celio Geraldo
Todeschini, Adriane
Rodrigues, Juliany Cola Fernandes
Palatnik-de-Sousa, Clarisa Beatriz
Morrot, Alexandre
Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
title Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
title_full Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
title_fullStr Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
title_full_unstemmed Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
title_short Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
title_sort expression of leukosialin (cd43) defines a major intrahepatic t cell subset associated with protective responses in visceral leishmaniasis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340829/
https://www.ncbi.nlm.nih.gov/pubmed/25874567
http://dx.doi.org/10.1186/s13071-015-0721-9
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