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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

IgG profile of serum antibodies toLeishmania(L.) infantum chagasiof CD43-deficient mice. Sera of CD43+/+ and CD43−/− mice infected with 5 × 107 amastigote forms of Leishmania (L.) infantum chagasi were collected at 30 DPI and the absorbance values of IgG antibody isotypes (IgG1, IgG2a and IgG2b) were determined by ELISA using Leishmania (L.) infantum chagasi promastigote lysates. Bars show levels of IgG1, IgG2a and IgG2b antibodies as the individual absorbancy values of 1/100 diluted sera. Asterisks indicate significant differences between groups ***(p < 0.001). Data represent the individual results for each group of mice of two independent experiments.
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Fig2: IgG profile of serum antibodies toLeishmania(L.) infantum chagasiof CD43-deficient mice. Sera of CD43+/+ and CD43−/− mice infected with 5 × 107 amastigote forms of Leishmania (L.) infantum chagasi were collected at 30 DPI and the absorbance values of IgG antibody isotypes (IgG1, IgG2a and IgG2b) were determined by ELISA using Leishmania (L.) infantum chagasi promastigote lysates. Bars show levels of IgG1, IgG2a and IgG2b antibodies as the individual absorbancy values of 1/100 diluted sera. Asterisks indicate significant differences between groups ***(p < 0.001). Data represent the individual results for each group of mice of two independent experiments.

Mentions: Resistance to visceral infection by Leishmania species is associated with the IgG isotype profile [23]. Hence, we measured specific IgG antibody levels in mouse serum to determine whether the impaired resistance of CD43-deficient mice is associated with a switch in the IgG subtype profile. Serum samples were collected at day 30 post-infection and IgG titers were determined by ELISA. We found that levels of IgG2a parasite-specific antibodies in infected CD43−/− mice were significantly lower than in infected wild-type mice (Figure 2). On the other hand, the IgG1 and IgG2b antibodies themselves, from both groups, did not differ significantly in their reactivity to lysates (Figure 2).Figure 2


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)

IgG profile of serum antibodies toLeishmania(L.) infantum chagasiof CD43-deficient mice. Sera of CD43+/+ and CD43−/− mice infected with 5 × 107 amastigote forms of Leishmania (L.) infantum chagasi were collected at 30 DPI and the absorbance values of IgG antibody isotypes (IgG1, IgG2a and IgG2b) were determined by ELISA using Leishmania (L.) infantum chagasi promastigote lysates. Bars show levels of IgG1, IgG2a and IgG2b antibodies as the individual absorbancy values of 1/100 diluted sera. Asterisks indicate significant differences between groups ***(p < 0.001). Data represent the individual results for each group of mice of two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: IgG profile of serum antibodies toLeishmania(L.) infantum chagasiof CD43-deficient mice. Sera of CD43+/+ and CD43−/− mice infected with 5 × 107 amastigote forms of Leishmania (L.) infantum chagasi were collected at 30 DPI and the absorbance values of IgG antibody isotypes (IgG1, IgG2a and IgG2b) were determined by ELISA using Leishmania (L.) infantum chagasi promastigote lysates. Bars show levels of IgG1, IgG2a and IgG2b antibodies as the individual absorbancy values of 1/100 diluted sera. Asterisks indicate significant differences between groups ***(p < 0.001). Data represent the individual results for each group of mice of two independent experiments.
Mentions: Resistance to visceral infection by Leishmania species is associated with the IgG isotype profile [23]. Hence, we measured specific IgG antibody levels in mouse serum to determine whether the impaired resistance of CD43-deficient mice is associated with a switch in the IgG subtype profile. Serum samples were collected at day 30 post-infection and IgG titers were determined by ELISA. We found that levels of IgG2a parasite-specific antibodies in infected CD43−/− mice were significantly lower than in infected wild-type mice (Figure 2). On the other hand, the IgG1 and IgG2b antibodies themselves, from both groups, did not differ significantly in their reactivity to lysates (Figure 2).Figure 2

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