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Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice.

Silva-Barrios, Sasha; Stäger, Simona (2019). Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice. European Journal of Immunology , vol. 49 . p. 1082-1091. DOI: 10.1002/eji.201847917.

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Résumé

Visceral leishmanisiais, a chornic, potentially fatal disease, is characterized by high production of low-affinity antibodies. In humans, hypergammaglobulinemia is prediction of disease progression. Nevertheless, the contribution of hypermutated and/or class-switched immunoglobulins to disease pathogenesis has never been studied. Using Aicda-/- mice and the experimental model of Leishmania donovani infection, we demonstrate that the absence of hypermutated and/or class-switched antibodies was associated with increased resistance to disease, stronger protective Th1 responses and a lower frequency of regulatory IFNγ+ IL-10+ CD4 T cells. Interestingly, stronger Th1 responses and the absence of IFNγ+ IL-10+ CD4 T cells during chronic infection in infected Aicda-/- mice was not caused by a T cell intrinsic effect of AID, but by changes in the cytokine environment during chronic disease. Indeed TNF, IL-10 and IFN-ß expressions were only upregulated in the presence of hypermutated, class-switched antibodies and hypergammaglobulinemia at later stages of infection. Taken together, our results suggest that hypergammaglobulinemia sustains inhibitory responses during chronic visceral leishmaniasis.

Type de document: Article
Mots-clés libres: AID; Leishmania donovani; T helper cells; hypergammaglobulinemia; regulatory T cells
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 janv. 2020 21:15
Dernière modification: 28 janv. 2020 21:15
URI: http://espace.inrs.ca/id/eprint/8215

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