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The role of intestinal antigen-presenting cells in generating T cell-mediated antifungal immunity

Project description

The intestinal antigen-presenting cells’ role in antifungal immunity

Intestinal fungi impact the immune system. Candida albicans is commonly found in the guts of most people, but the immune system typically keeps it under control. However, immunodeficient patients often suffer from candidiasis, which poses a challenge for treatment: Candida albicans can trigger a protective Th17 response, and studies show potential involvement in asthma and rheumatoid arthritis. The initial stages of immune responses against intestinal fungi are not well understood. The EU-funded Candida Immunity Project aims to uncover the antigen-presenting cells responsible for the Th17 response during Candida colonisation. It will employ single-cell RNA sequencing to identify Candida-responsive populations, shedding light on the early phases of the antifungal response by analysing communication between Candida and antigen-presenting cells in mice.

Objective

Intestinal fungi are an important component of the microbiome and their homeostasis/dysbiosis constantly shapes the immune responses. The human commensal fungus Candida albicans colonizes the gut of 40-80% of individuals. However, life-threatening infections caused by this fungus are relatively rare since the unwinding of its pathogenic potential is kept in check by the immune system. In line with this, immunodeficient patients suffer often from Candidiasis, which is typically difficult to treat. Candida albicans induce strong Th17 response which is the main protective mechanism against pathogenic fungi. Candida-induced Th17 cells can protect the host not only against other fungal but also against extracellular pathogens. Besides the positive effects of Th17 in defence against pathogens, recent studies connect fungi-elicited Th17 response with local and gut-distal pathologies such as asthma, multiple sclerosis, Crohn’s disease, or rheumatoid arthritis. Despite that the role of Th17 is relatively well studied, the early events at the initiation of innate and adaptive immune responses against intestinal fungi are much less known. Various mutations in the adaptive immune system are clearly associated with impaired antifungal immunity. The proposed project will fill this knowledge gap by systematic studies of antigen-presenting cells involved in initiating Th17 response upon Candida colonization. We propose to use single-cell RNA sequencing techniques to determine Candida responsive populations followed by deletion of MHCII on selected APCs populations to prove that the effect is mediated via antigen presentation. We will further study the bidirectional interaction between Candida and APCs in these mice. This study will lead to the understanding of events at the beginning of antifungal response via the identification of cell type(s) responsible for Th17 induction as well as the regulation of fungal homeostasis and control of Candida virulence.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-WIDERA-2022-TALENTS-04

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Coordinator

UNIVERZITA KARLOVA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 166 278,72
Address
OVOCNY TRH 560/5
116 36 Praha 1
Czechia

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Region
Česko Praha Hlavní město Praha
Activity type
Higher or Secondary Education Establishments
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Total cost

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