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

Nico D, Maran N, Santos L, Ramos-Junior ES, Mantuano NR, Coutinho JL, Vale AM, Freire-de-Lima CG, Todeschini A, Rodrigues JC, Palatnik-de-Sousa CB, Morrot A - Parasit Vectors (2015)

Bottom Line: IFN-γ-producing T cells are involved in protection against the disease.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.Our findings point to a role of CD43 in the development of host resistance to visceral leishmaniasis.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro (UFRJ), CCS - Sala D1-035, Av. Carlos Chagas Filho, 373 - Cidade Universitária, CEP 21.941-902, Ilha do Fundão, Rio de Janeiro, RJ, Brazil. morrot@micro.ufrj.br.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Expression of CD43+T cells defines major intrahepatic CD4+and CD8+T cell subsets during visceral leishmaniasis. Following infection of CD43+/+ and CD43−/− mice with 5 × 107amastigotes of Leishmania (L.) infantum chagasi, spleens and livers were collected at 30 DPI for FACS analysis. Splenocytes and mononuclear cells purified from livers were analyzed by FACS after staining with anti-CD43-FITC, anti-CD8-APC and anti-CD4-PE. Plots represent CD43+CD8+ and CD43+CD4+ lymphocyte pools derived from five mice. The values in the corners represent mean percentages of CD43+ cells in the total CD4+ or CD8+ T cell populations. Non-infected mice were used as controls. These data are representative of three independent experiments, using five mice per group.
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Fig4: Expression of CD43+T cells defines major intrahepatic CD4+and CD8+T cell subsets during visceral leishmaniasis. Following infection of CD43+/+ and CD43−/− mice with 5 × 107amastigotes of Leishmania (L.) infantum chagasi, spleens and livers were collected at 30 DPI for FACS analysis. Splenocytes and mononuclear cells purified from livers were analyzed by FACS after staining with anti-CD43-FITC, anti-CD8-APC and anti-CD4-PE. Plots represent CD43+CD8+ and CD43+CD4+ lymphocyte pools derived from five mice. The values in the corners represent mean percentages of CD43+ cells in the total CD4+ or CD8+ T cell populations. Non-infected mice were used as controls. These data are representative of three independent experiments, using five mice per group.

Mentions: We next examined whether the increased parasite load associated with absence of CD43 influenced the tissue distribution of intrahepatic T cells. It has been demonstrated that T cell- and lymphokine-dependent mechanisms are involved in the formation of antileishmanial tissue granulomas and the acquisition of resistance to Leishmania infection [22]. Hence we performed experiments to characterize the phenotypic distribution of intrahepatic T cells based on expression of the CD43 marker. In these experiments, wild-type mice were infected with amastigote forms of Leishmania (L.) infantum chagasi and the presence of CD4+ and CD8+ T cells in the spleen and liver was evaluated by FACS at 30 days post-infection. In both naïve and infected mice, the CD43+ subset in the CD4+ T cell compartment was significantly smaller than the CD43− population whereas in the CD8+ T cell compartment, the majority of cells expressed CD43 (Figure 4). A striking difference became apparent when we examined the expression of CD43 in the intrahepatic CD4+ T cell population during infection, as our data indicated that the majority of the CD4+ T cells, like the CD8+ T cells, were CD43+ (Figure 4).Figure 4


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

Nico D, Maran N, Santos L, Ramos-Junior ES, Mantuano NR, Coutinho JL, Vale AM, Freire-de-Lima CG, Todeschini A, Rodrigues JC, Palatnik-de-Sousa CB, Morrot A - Parasit Vectors (2015)

Expression of CD43+T cells defines major intrahepatic CD4+and CD8+T cell subsets during visceral leishmaniasis. Following infection of CD43+/+ and CD43−/− mice with 5 × 107amastigotes of Leishmania (L.) infantum chagasi, spleens and livers were collected at 30 DPI for FACS analysis. Splenocytes and mononuclear cells purified from livers were analyzed by FACS after staining with anti-CD43-FITC, anti-CD8-APC and anti-CD4-PE. Plots represent CD43+CD8+ and CD43+CD4+ lymphocyte pools derived from five mice. The values in the corners represent mean percentages of CD43+ cells in the total CD4+ or CD8+ T cell populations. Non-infected mice were used as controls. These data are representative of three independent experiments, using five mice per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340829&req=5

Fig4: Expression of CD43+T cells defines major intrahepatic CD4+and CD8+T cell subsets during visceral leishmaniasis. Following infection of CD43+/+ and CD43−/− mice with 5 × 107amastigotes of Leishmania (L.) infantum chagasi, spleens and livers were collected at 30 DPI for FACS analysis. Splenocytes and mononuclear cells purified from livers were analyzed by FACS after staining with anti-CD43-FITC, anti-CD8-APC and anti-CD4-PE. Plots represent CD43+CD8+ and CD43+CD4+ lymphocyte pools derived from five mice. The values in the corners represent mean percentages of CD43+ cells in the total CD4+ or CD8+ T cell populations. Non-infected mice were used as controls. These data are representative of three independent experiments, using five mice per group.
Mentions: We next examined whether the increased parasite load associated with absence of CD43 influenced the tissue distribution of intrahepatic T cells. It has been demonstrated that T cell- and lymphokine-dependent mechanisms are involved in the formation of antileishmanial tissue granulomas and the acquisition of resistance to Leishmania infection [22]. Hence we performed experiments to characterize the phenotypic distribution of intrahepatic T cells based on expression of the CD43 marker. In these experiments, wild-type mice were infected with amastigote forms of Leishmania (L.) infantum chagasi and the presence of CD4+ and CD8+ T cells in the spleen and liver was evaluated by FACS at 30 days post-infection. In both naïve and infected mice, the CD43+ subset in the CD4+ T cell compartment was significantly smaller than the CD43− population whereas in the CD8+ T cell compartment, the majority of cells expressed CD43 (Figure 4). A striking difference became apparent when we examined the expression of CD43 in the intrahepatic CD4+ T cell population during infection, as our data indicated that the majority of the CD4+ T cells, like the CD8+ T cells, were CD43+ (Figure 4).Figure 4

Bottom Line: IFN-γ-producing T cells are involved in protection against the disease.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.Our findings point to a role of CD43 in the development of host resistance to visceral leishmaniasis.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro (UFRJ), CCS - Sala D1-035, Av. Carlos Chagas Filho, 373 - Cidade Universitária, CEP 21.941-902, Ilha do Fundão, Rio de Janeiro, RJ, Brazil. morrot@micro.ufrj.br.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus