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Project

Scrutinizing the role of mast cells during human and murine Leishmania infections

Despite a global distribution of Leishmaniasis and 1.5 to 2 million new cases annually, no effective human vaccines are available and treatment failure with current drugs is on the rise. Mast cells (MCs) are immune sentinels in the skin that are amongst the first to contact the Leishmania parasite following a sand fly bite. These cells play major roles in orchestrating early inflammatory responses, regulating vascular permeability and influencing immunity development in lymph nodes. Despite seminal work in mosquito-transmitted viral diseases, MCs remain underexplored as target cell during parasitic infections. Combining the strengths in immunology, parasitology, transcriptomics and biostatistics, the role of MCs will be assessed in natural Leishmania infection. Combining digital transcriptomic data from large human cohorts and experimental mouse infections, will enable detailed cross-species and multi-tissue insights into MC responses across the whole clinical spectrum of leishmaniasis. Using human MCs derived from progenitors in donor blood, a battery of cellular activation markers and specific silencing of MC gene expression using an in-house, cutting-edge method will enable unprecedented mechanistic insights in the interaction with infectious agents, i.e. Leishmania spp. parasites. This may provide new biomarkers for clinical follow-up as well as novel therapeutic targets that will be explored in the appropriate animal models of leishmaniasis initiated by a sand fly bite.

Date:1 Jan 2021 →  Today
Keywords:Leishmania infection, Mast cells (MCs)
Disciplines:Tropical medicine, Public health sciences not elsewhere classified, Immunology not elsewhere classified, Biomarker discovery and evaluation not elsewhere classified, Biostatistics