RGD Reference Report - Hypergammaglobulinemia sustains the development of regulatory responses during chronic Leishmania donovani infection in mice. - Rat Genome Database

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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.
RGD ID: 32716386
Pubmed: PMID:31001826   (View Abstract at PubMed)
DOI: DOI:10.1002/eji.201847917   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AICDAHumanvisceral leishmaniasis  ISOAicda (Mus musculus)mRNA:altered expression:Bcell and CD4TcellRGD 
AicdaRatvisceral leishmaniasis  ISOAicda (Mus musculus)mRNA:altered expression:Bcell and CD4TcellRGD 
AicdaMousevisceral leishmaniasis  IEP mRNA:altered expression:Bcell and CD4TcellRGD 
AicdaMousevisceral leishmaniasis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aicda  (activation-induced cytidine deaminase)

Genes (Mus musculus)
Aicda  (activation-induced cytidine deaminase)

Genes (Homo sapiens)
AICDA  (activation induced cytidine deaminase)


Additional Information