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

Authors: Silva-Barrios, Sasha  Stäger, Simona 
Citation: Silva-Barrios S and Stäger S, Eur J Immunol. 2019 Jul;49(7):1082-1091. doi: 10.1002/eji.201847917. Epub 2019 May 23.
Pubmed: (View Article at PubMed) PMID:31001826
DOI: Full-text: DOI:10.1002/eji.201847917

Visceral leishmaniasis, a chronic, 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 were 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.

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CRRD Object Information
CRRD ID: 32716386
Created: 2020-06-26
Species: All species
Last Modified: 2020-06-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.