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DFG project G:(GEPRIS)222306032
The role of mast cells for directing T cell-dependent immunity in cutaneous leishmaniasis
| Coordinator | Professorin Dr. Ruth Esther von Stebut-Borschitz |
| Grant period | 2012 - 2017 |
| Funding body | Deutsche Forschungsgemeinschaft |
| DFG | |
| Identifier | G:(GEPRIS)222306032 |
⇧ SPP 1394: Mast-cells - promoters of health and modulators of disease ⇧
Note: Leishmaniasis is a parasitic disease with ~12 million infected people worldwide. We have previously shown that MC are also involved in the control of infections with the parasite Leishmania major. Intradermal inoculation of physiologically relevant low doses of L. major resulted in local MC activation and genetically MC-deficient KitwIKitw-v, KitW-sh/KitW-sh as well as Mcpt5xiDTR mice treated with DT to delete MC displayed significantly worsened disease with larger skin lesions. In addition, MC deficiency was associated with higher lesional parasite burdens, enhanced visceralization and predominant detrimental Th2/Th17/Treg immune responses. We now intend to study the mechanism of action by analysing the direct contribution of MC to antigen presentation and T cell education. In addition, we will assess the role of MCderived factors and the interaction of MC with antigen presenting cells (e.g. dendritic cells) and/or T cells in vivo using sophisticated mouse models involving bone marrow chimeras combining MC and DC deficiency and/or selective deletion of e.g. MHC class II, CD40L or cytokines from MC. In the long run, modulation of MC function may allow for a modification of disease outcome in infections with this important human pathogen.