Leishmania parasites are protozoan pathogens which are transmitted by sand flies to various mammalian hosts, where they cause a broad range of diseases ranging from local and ultimately self-healing lesions to systemic, visceral infections that are lethal, if untreated. Studies with well-established mouse models of leishmaniasis revealed that both the innate and adaptive immune system (macrophages, dendritic cells (DCs), natural killer (NK) cells, CD4+ T helper (Th) cells, CD8+ T cells, B lymphocytes and different cytokines such as IFN-g, TNF and type I inferferons) contribute to an efficient immune response against the intracellular parasites.
The focus of our research work is the analysis of cells, receptors, cytokines and antimicrobial effector mechanisms of the innate immune system during Leishmania infections. Using high resolution imaging techniques, genetic approaches, immunophysical methods and mouse models we aim to elucidate the immunological processes and the tissue micromilieu that account for the control or evasion of the intracellular protozoan parasites Leishmania major, Leishmania tropica, Leishmania infantum, Leishmania mexicana and Leishmania braziliensis and to define novel approaches for the treatment of human leishmaniasis.
In current projects special emphasis is given to the
A) function and regulation of arginase 1, arginase 2 and inducible nitric oxide synthase (iNOS, NOS2) during cutaneous leishmaniasis (L. major and L. mexicana) (supported by the German Research Foundation, SFB 1181 “Checkpoints for resolution of inflammation”, project C4)
B) epigenetic regulation of arginase 1 by tumor necrosis factor (TNF) and interferon-g in visceral leishmaniasis (L. infantum) (Infect-EraNet, EU/BMBF)
C) mechanisms of TNF-mediated control of intracellular pathogens in mice and man (supported by the Interdisciplinary Center for Clinical Research, University Hospital of Erlangen, project A63)
D) crossregulation of inducible nitric oxide synthase (iNOS, NOS2) and iron in cutaneous and visceral leishmaniasis
E) Toll-like receptor 9-dependent regulation of the immune response in visceral leishmaniasis (L. infantum) (supported by the German Research Foundation, Research Training Group 1660, project A5)
F) role of natural killer cells and innate lymphoid cells (ILC1, ILC2) during cutaneous (L. major) and visceral (L. infantum) infection (supported by the German Research Foundation, SPP 1937 “Innate lymphoid cells”)
G) therapeutic and immunoregulatory effects of reactive chlorine oxygen species in human cutaneous leishmaniasis (together with Waisenmedizin e.V. Freiburg https://waisenmedizin.org/ )
Recent key publications