AG Adjobimey

Summary

One of the fascinating properties of helminth parasites is their capacity to manipulate their host’s immune system to guarantee their own survival. Their evasion strategies have evolved during centuries of adaptation to reach levels near perfection. In addition of supporting parasite survival, helminth-induced immunoregulatory mechanisms profoundly impact the “immunophysiopathology” of other infections.

Our Group is undertaking fundamental research into the mechanisms of parasite induced immune tolerance and how these can be modulated by co-infections and additional immune activation.

We are interested in understanding how T cell subsets and B cells, central effectors of adaptive immune responses interact in the context of helminth infections and how this contributes to the decision towards tolerance, immunity or pathology. Towards this goal, we dissect the cellular and molecular interactions that lead to the production and secretion of the non cytolytic antibody IgG4 and how this immunoregulated phenotype is modulated by additional innate signals like Toll and NOD receptors activation.

Our recent findings suggest that, strong parasite specific Th2 responses combined with robust parasite-independent Th17 polarization in the absence of adequate immune regulation is associated with hyper-responsive sever forms of human onchocerciasis.

We have also unraveled new Treg: B cells conversations, involving IL-10, TGF-beta and GITR and GITRL signaling and have demonstrated that Tregs cells can suppress B cells activation and differentiation into plasma cells, while modulating their antibody secretion. This suppression of B cells by Tregs leads to the preferential secretion of IgG4 and is reversed by TLR-ligands triggering of the B cells, which in turn convert Foxp3+ Treg cells into Foxp3+ IL-17 secreting T cells.

Our research interest also encompasses the investigation of how engagement of FcyR by IgG/IgG4 –Antigen immune complexes impacts activation of effector cells such as eosinophils, basophils and neutrophils.

We believe that the elucidation of how helminths manipulate immune cells will in the future provide us with new tools to promote novel therapeutical strategies to control immunopathology, not only in parasitic infections, but also in allergies and other inflammatory disorders.

 

Publications

Katawa G, Layland LE, Debrah AY, von Horn C, Batsa L, Kwarteng A, Arriens S, Taylor DW, Specht S, Hoerauf A, Adjobimey T. Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells. PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3414. doi:10.1371/journal.pntd.0003414. eCollection 2015 Jan. PubMed PMID: 25569210.

Adjobimey T.,Satoguina T.,Oldenburg J.,Hoerauf A.andLayland LE. Co-activation through TLR4 and TLR9 but not TLR2 skews Treg-mediated modulation of immunogobulins and induces IL-17-secretion in Treg:B cell co-cultures. Innate Immunity (2013). PubMed PMID 23529856.

Arndts, K., Deininger, S., Specht, S., Klarmann, U., Mand, S., Adjobimey, T., Debrah, A. Y., Batsa, L., Kwarteng, A., Epp, C., Taylor, M., Adjei, O., Layland, L. E. & Hoerauf, A. Elevated Adaptive Immune Responses Are Associated with Latent Infections of Wuchereria bancrofti. PLoS Negl Trop Dis, 6, (2012) e1611. PubMed PMID: 22509424.

Adjobimey T., Hoerauf A., Induction of immunoglobulin G4 in human filariasis: an indicator of immunoregulation.  Ann Trop Med Parasitol 104 (6) (2010) 455-464. PubMed PMID: 20863434.

Satoguina J.S., Adjobimey T., Arndts, K., Hoch J., Oldenburg, J., Layland L.E. and Hoerauf A. 2008. Tr-1-and Naturally-Occurring regulatory T cells induce IgG4 in B cells through GITR/GITRL interaction, IL-10 and TGF-β. Eur. J. Immunol 38(11) (2008) 3101-13. PubMed PMID: 18924213.

 

Funding

DFG

DAAD

BONFOR

Date: 
Thursday, April 16, 2015 - 14:22 - Saturday, July 25, 2015 - 14:22

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