Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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. This article is protected by copyright. All rights reserved.
Document type :
Journal articles
Complete list of metadatas

https://hal-riip.archives-ouvertes.fr/pasteur-02133228
Contributor : Michel Courcelles <>
Submitted on : Friday, May 17, 2019 - 8:20:33 PM
Last modification on : Wednesday, May 29, 2019 - 4:26:35 PM

Identifiers

Collections

Citation

Sasha Silva-Barrios, Simona Stäger. Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice. European Journal of Immunology, Wiley-VCH Verlag, 2019, 26 (12), pp.3246-3256.e4. ⟨10.1002/eji.201847917⟩. ⟨pasteur-02133228⟩

Share

Metrics

Record views

27