TY - JOUR
T1 - Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis
AU - Nico, Dirlei
AU - Maran, Naiara
AU - Santos, Leonardo
AU - Ramos-Junior, Erivan Schnaider
AU - Mantuano, Natália Rodrigues
AU - Coutinho, Joseane Lima Prado
AU - Vale, Andre Macedo
AU - Freire-De-Lima, Celio Geraldo
AU - Todeschini, Adriane
AU - Rodrigues, Juliany Cola Fernandes
AU - Palatnik-De-Sousa, Clarisa Beatriz
AU - Morrot, Alexandre
N1 - Publisher Copyright:
© 2015 Nico et al.; licensee BioMed Central.
PY - 2015
Y1 - 2015
N2 - 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 × 107 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.
AB - 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 × 107 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.
KW - Host protective responses
KW - Intrahepatic T cell subsets
KW - Leishmania (L.) infantum chagasi
KW - Leukosialin (cd43)
KW - Visceral leishmaniasis
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U2 - 10.1186/s13071-015-0721-9
DO - 10.1186/s13071-015-0721-9
M3 - Article
C2 - 25874567
AN - SCOPUS:84928692202
SN - 1756-3305
VL - 8
JO - Parasites and Vectors
JF - Parasites and Vectors
IS - 1
M1 - 111
ER -