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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

CD43 deficient mice are susceptible to visceral leishmaniasis. 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. (A) Infection in CD43-deficient mice results in an impaired DTH response. The vertical axis in the histogram represents the individual values of the thickness of the skin reaction in mm 24 h and 48 h after intradermal injection of 107 freeze–thawed stationary phase promastigotes at 30 DPI. Controls with saline were done by contra-lateral injection and their values were subtracted from the reaction promoted by Leishmania antigen. (B) Liver/body relative weights are increased in infected CD43-deficient mice. The body weight was measured in grams at day 30 and the liver/body relative weights (grams of organ weight × 100 / grams of body weight) were determined in CD43+/+ and CD43−/− mice. (C) Increased parasite burden in the liver of CD43-deficient mice. The vertical axis in the histogram represents the average liver parasite load in Leishman-Donovan units of Stauber (LDU = number of amastigotes / 1000 cell nuclei × organ weight in mg) obtained at 30 DPI. Data are means ± SE and represent the results of three independent experiments performed with 5–6 mice per treatment. Differences between groups are significant *(p < 0.05).
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Fig1: CD43 deficient mice are susceptible to visceral leishmaniasis. 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. (A) Infection in CD43-deficient mice results in an impaired DTH response. The vertical axis in the histogram represents the individual values of the thickness of the skin reaction in mm 24 h and 48 h after intradermal injection of 107 freeze–thawed stationary phase promastigotes at 30 DPI. Controls with saline were done by contra-lateral injection and their values were subtracted from the reaction promoted by Leishmania antigen. (B) Liver/body relative weights are increased in infected CD43-deficient mice. The body weight was measured in grams at day 30 and the liver/body relative weights (grams of organ weight × 100 / grams of body weight) were determined in CD43+/+ and CD43−/− mice. (C) Increased parasite burden in the liver of CD43-deficient mice. The vertical axis in the histogram represents the average liver parasite load in Leishman-Donovan units of Stauber (LDU = number of amastigotes / 1000 cell nuclei × organ weight in mg) obtained at 30 DPI. Data are means ± SE and represent the results of three independent experiments performed with 5–6 mice per treatment. Differences between groups are significant *(p < 0.05).

Mentions: We observed a lower DTH response to the promastigote leishmania antigen in CD43−/− mice on a C57BL/6 background than in wild type C57BL/6 mice after infection with Leishmania (L.) infantum chagasi (Figure 1A). These data indicate that cellular immunity against visceral infection of leishmania parasite is impaired in knockout mice, raising the possibility that CD43 is required for optimal development of host resistance to VL. We next examined the signs of acute infection in the liver. Following intravenous infection with amastigote forms of Leishmania (L.) infantum chagasi we observed that the increased susceptibility of CD43-deficient mice was correlated with greater increases in the liver/body weight ratio (Figure 1B) and intrahepatic parasite burden at 30 days post-infection in CD43−/− mice than in the wild-type control mice (Figure 1C).Figure 1


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)

CD43 deficient mice are susceptible to visceral leishmaniasis. 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. (A) Infection in CD43-deficient mice results in an impaired DTH response. The vertical axis in the histogram represents the individual values of the thickness of the skin reaction in mm 24 h and 48 h after intradermal injection of 107 freeze–thawed stationary phase promastigotes at 30 DPI. Controls with saline were done by contra-lateral injection and their values were subtracted from the reaction promoted by Leishmania antigen. (B) Liver/body relative weights are increased in infected CD43-deficient mice. The body weight was measured in grams at day 30 and the liver/body relative weights (grams of organ weight × 100 / grams of body weight) were determined in CD43+/+ and CD43−/− mice. (C) Increased parasite burden in the liver of CD43-deficient mice. The vertical axis in the histogram represents the average liver parasite load in Leishman-Donovan units of Stauber (LDU = number of amastigotes / 1000 cell nuclei × organ weight in mg) obtained at 30 DPI. Data are means ± SE and represent the results of three independent experiments performed with 5–6 mice per treatment. Differences between groups are significant *(p < 0.05).
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Related In: Results  -  Collection

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Fig1: CD43 deficient mice are susceptible to visceral leishmaniasis. 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. (A) Infection in CD43-deficient mice results in an impaired DTH response. The vertical axis in the histogram represents the individual values of the thickness of the skin reaction in mm 24 h and 48 h after intradermal injection of 107 freeze–thawed stationary phase promastigotes at 30 DPI. Controls with saline were done by contra-lateral injection and their values were subtracted from the reaction promoted by Leishmania antigen. (B) Liver/body relative weights are increased in infected CD43-deficient mice. The body weight was measured in grams at day 30 and the liver/body relative weights (grams of organ weight × 100 / grams of body weight) were determined in CD43+/+ and CD43−/− mice. (C) Increased parasite burden in the liver of CD43-deficient mice. The vertical axis in the histogram represents the average liver parasite load in Leishman-Donovan units of Stauber (LDU = number of amastigotes / 1000 cell nuclei × organ weight in mg) obtained at 30 DPI. Data are means ± SE and represent the results of three independent experiments performed with 5–6 mice per treatment. Differences between groups are significant *(p < 0.05).
Mentions: We observed a lower DTH response to the promastigote leishmania antigen in CD43−/− mice on a C57BL/6 background than in wild type C57BL/6 mice after infection with Leishmania (L.) infantum chagasi (Figure 1A). These data indicate that cellular immunity against visceral infection of leishmania parasite is impaired in knockout mice, raising the possibility that CD43 is required for optimal development of host resistance to VL. We next examined the signs of acute infection in the liver. Following intravenous infection with amastigote forms of Leishmania (L.) infantum chagasi we observed that the increased susceptibility of CD43-deficient mice was correlated with greater increases in the liver/body weight ratio (Figure 1B) and intrahepatic parasite burden at 30 days post-infection in CD43−/− mice than in the wild-type control mice (Figure 1C).Figure 1

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