Project Details
Projekt
Innate lymphoid cells in mouse and human leishmaniasis
Subject Area
Immunology
Term
since 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 320380481
Innate lymphoid cells (ILC) exert important regulatory and helper functions in the immune system. While the role of ILCs has already been studied quite extensively in helminth and bacterial intestinal infections, little is known about their function in protozoan infections such as cutaneous (CL) and visceral leishmaniasis (VL). In our previous mouse studies we found that both classical natural killer (cNK) cells (also known as cytotoxic ILC1) and non-cytotoxic ILC1 rapidly produced protective interferon (IFN)-gamma in response to Leishmania (L.) major (CL) or L. infantum (VL) in an interleukin (IL)-12/IL-18-dependent manner. In contrast, ILC2 neither became activated for cytokine production (IL-4/IL-13) nor expanded numerically at the site of parasite inoculation during the innate phase of infection, not even in L. major-infected BALB/c mice, which develop systemic disease due to a sustained activity of type 2 T helper (Th2) cells. Similar to the mouse model Leishmania parasites of various species (including L. major and L. infantum) also caused human NK cell activation, which required direct contact between NK cells and monocytes and transpresentation of IL-18. In the present proposal we will test the new hypothesis that cutaneous or visceral infections with Leishmania parasites affect the development, expansion and/or function of both mouse and human ILC. Specifically, we aim (1) to investigate whether IFN-gamma and/or type I IFNs (IFN-alpha/beta) suppress the proliferation and function of ILC2 during the innate phase of L. major and L. infantum infection so that these cells become only relevant during the phase of clinical resolution when IFN-gamma and IFN-alpha/beta are downregulated; (2) to examine whether Leishmania parasites or parasite-derived products affect the development, expansion and/or function of mouse and human ILC; and (3) to determine the phenotype, frequency, tissue distribution and the cell-cell contacts of the different ILC subtypes in skin lesions of patients with different forms of cutaneous leishmaniasis as compared to normal skin samples. We are convinced that the proposed analyses will provide important and new insights into the relevance of ILC for parasitic diseases and skin infections.
DFG Programme
Priority Programmes
Subproject of
SPP 1937:
Innate Lymphoid Cells
