Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice. Issue 7 (23rd May 2019)

• Record Type: Journal Article
• Authors: Silva‐Barrios, Sasha; Stäger, Simona
• Is Part Of: European journal of immunology. Volume 49:Issue 7(2019)
• Page Start: 1082
• Page End: 1091
• Publication Date: 2019-05-23
• Subjects: AID -- hypergammaglobulinemia -- Leishmania donovani -- regulatory T cells -- T helper cells; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847917
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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. Abstract : Hypergammaglobulinemia, induced by the protozoan parasite Leishmania donovani, promotes disease exacerbation by enhancing IL‐10, TNF, and IFN‐I expression, favoring Tr1 development, and inhibiting protective Th1 responses.