PYRAMID | PYHIN-Regulated Memory T cell protection for Infectious Diseases

Summary
Pyrin and HIN domain (PYHIN) proteins play an integral role in the innate immune response to DNA and RNA viruses via direct detection of viral DNA and transcriptional regulation of pro-inflammatory and anti-viral cytokines respectively. Although expressed by various cells of the myeloid lineage, including some classical antigen presenting cells, the role of PYHINs in the context of T cell-mediated adaptive immunity has yet to be investigated. This project aims to elucidate how PYHIN proteins modulate acute and long-term CD8+ memory T cell responses to influenza A virus (IAV), a respiratory RNA virus which causes significant morbidity and mortality annually. Current seasonal IAV vaccines, exhibit variable efficacy and the neutralising antibodies they induce cannot protect against alternative IAV strains, particularly those with pandemic potential. In contrast, IAV-specific CD8+ memory T cells can elicit such cross-protective immunity by targeting conserved viral proteins, thus making the identification of mechanisms which give rise to these cells high priority in the search for a universal IAV vaccine. Herein, we will perform in-depth characterisation of PYHIN expression in human and murine dendritic cells. We will also perform genetic manipulation of PYHIN expression in primary immune cells to interrogate functionality and undertake infection studies in transgenic mice lacking certain PYHIN family members to determine their role in the formation of IAV-specific T cell memory in vivo. Overall, this project is extremely timely, providing crucial mechanistic insight which can inform rational vaccine design aimed at eliciting cross-protective T cell responses to respiratory RNA viruses.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101031022
Start date: 01-09-2021
End date: 31-08-2023
Total budget - Public funding: 184 590,72 Euro - 184 590,00 Euro
Cordis data

Original description

Pyrin and HIN domain (PYHIN) proteins play an integral role in the innate immune response to DNA and RNA viruses via direct detection of viral DNA and transcriptional regulation of pro-inflammatory and anti-viral cytokines respectively. Although expressed by various cells of the myeloid lineage, including some classical antigen presenting cells, the role of PYHINs in the context of T cell-mediated adaptive immunity has yet to be investigated. This project aims to elucidate how PYHIN proteins modulate acute and long-term CD8+ memory T cell responses to influenza A virus (IAV), a respiratory RNA virus which causes significant morbidity and mortality annually. Current seasonal IAV vaccines, exhibit variable efficacy and the neutralising antibodies they induce cannot protect against alternative IAV strains, particularly those with pandemic potential. In contrast, IAV-specific CD8+ memory T cells can elicit such cross-protective immunity by targeting conserved viral proteins, thus making the identification of mechanisms which give rise to these cells high priority in the search for a universal IAV vaccine. Herein, we will perform in-depth characterisation of PYHIN expression in human and murine dendritic cells. We will also perform genetic manipulation of PYHIN expression in primary immune cells to interrogate functionality and undertake infection studies in transgenic mice lacking certain PYHIN family members to determine their role in the formation of IAV-specific T cell memory in vivo. Overall, this project is extremely timely, providing crucial mechanistic insight which can inform rational vaccine design aimed at eliciting cross-protective T cell responses to respiratory RNA viruses.

Status

CLOSED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2020
MSCA-IF-2020 Individual Fellowships