Characterization of phenotype and function of innate lymphoid cells in cutaneous leishmaniasis

• Applicant: Professorin Dr. Ruth Esther von Stebut-Borschitz
• Subject Area: Dermatology ; Parasitology and Biology of Tropical Infectious Disease Pathogens ; Cell Biology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 320429358

Leishmaniasis is a disease observed after inoculation of a protozoan parasite into the skin inducing symptoms ranging from local, self-limiting lesions to life-threatening visceralisation. Protective immunity against Leishmania is mediated by antigen specific CD8+ and CD4+ T cells which are primed by infected dendritic cells (DC). However, decisions about resistance/susceptibility are made within a few days post infection suggesting an important role for innate effector cells. The role of the innate lymphocyte compartment for protection and regulation of the local immune response is poorly understood. Therefore, we aim to further define the phenotype and function of innate lymphoid cells (ILCs) and NK cells in L. major infections. ILC2 are the predominant ILC subsets in steady state in skin, however, we found that L. major infection leads to a loss of ILC2s while inducing NK cell and ILC1 activation in the infected skin. In the present proposal, after a detailed characterization of the frequency and phenotype of ILCs during infection, we have two major aims: We plan to i) characterize the mechanisms and relevance of ILC1 and NK cell activation, and ii) to investigate the mechanism leading to ILC2 loss, and iii) to restore the ILC2 presence in L. major lesions in order to examine the role of ILC2 during the course of infection. ILC2 may be important for healing and tissue integrity, whereas ILC1 and NK cells may contribute to proper Th priming and parasite elimination. Using a physiologically relevant low dose inoculum, we aim to characterize the role ILCs play for protection against this important human pathogen.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1937: Innate Lymphoid Cells