Leishmania-Infected MHC Class IIhigh Dendritic Cells Polarize CD4(+) T Cells toward a Nonprotective T-bet(+) IFN-gamma(+) IL-10(+) Phenotype

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Mariana Resende (Autor) Outra; Diana Moreira (Autor) Outra; Jorge Augusto (Autor) Outra; Joana Cunha (Autor) Outra; Bruno Neves (Autor) Outra; Maria Teresa Cruz (Autor) Outra; Jerome Estaquier (Autor) Outra; Anabela Cordeiro da Silva (Autor) FFUP; Ricardo Silvestre (Autor) Outra

Revista

Título: Journal of Immunology

Vol. 191

Páginas: 262-273

ISSN: 0022-1767

Editora: American Association of Immunologists

Indexação

ISI Web of Knowledge - 19 Citações

Scopus - 26 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-006-9Q9

DOI: 10.4049/jimmunol.1203518

Abstract (EN): A differential behavior among infected and bystander dendritic cells (DCs) has been explored in different infection models. We have analyzed both populations sorted on contact with visceral Leishmania infantum on a susceptible mice model evaluating the subsequent repercussions on adaptive immune response. Our results demonstrate a clear dichotomy between the immunomodulatory abilities of bystander and infected DCs. The bystander population presents increased levels of IL-12p40 and costimulatory molecules being capable to induce CD4(+) T cell activation with immune protective capabilities. In contrast, infected DCs, which express lower costimulatory molecules and higher levels of IL-10, promote the development of Leishmania Ag-specific, non-protective T-bet(+)IFN-gamma+IL-10(+) CD4(+) T cells with an effector phenotype. This specific polarization was found to be dependent on IL-12p70. Splenic infected DCs recovered from chronic infected animals are similarly capable to polarize ex vivo syngeneic naive CD4(+) T cells toward a T-bet(+)IFN-gamma+IL-10(+) phenotype. Further analysis revealed that only MHC class IIhigh-infected DCs were responsible for this polarization. The adoptive transfer of such polarized CD4(+) T cells facilitates visceral leishmaniasis in BALB/c mice in a clear contrast with their counterpart generated with bystander DCs that significantly potentiate protection. Further, we demonstrated that CD4(+) T cells primed by infected DCs in an IL-10 free system, thus deprived of T-bet(+)IFN-gamma+IL-10(+) population, restore the immune response and reduce parasite load, supporting a deleterious role of IFN-gamma+IL-10(+) T cells in the maintenance of infection. Overall, our results highlight novel subversion mechanisms by which nonprotective T-bet(+)IFN-gamma+IL-10(+) T cells are associated with chronicity and prolonged parasite persistence.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12