RA-COVID-19 V12 - Recherche - Action Coronavirus disease 2019 - Vague 12

Roles of type I interferons and plasmacytoid dendritic cells in Covid19 – RIPCOV

Roles of type I interferons and plasmacytoid dendritic cells in Covid19

In order to understand what causes severe cases of Covid19, and thus improve their medical management, it is essential to better understand the natural history of this disease caused by the coronavirus SARS-CoV2.

Roles of pDCs and IFN-I.

Specifically, we propose to solve the much debated role of type I interferons (IFN-I) and of plasmacytoid dendritic cells (pDCs) that are the major source of IFN-I during many viral infections.

We will take advantage of mutant SARS-Cov2 mouse models, which develop a disease very similar to Covid19, and which are modified in such a way that they enable tracing or depleting pDCs in vivo and following IFN-I producing cells with a high degree of resolution. This approach will allow testing the hypothesis that IFN-I and pDCs may play either a beneficial or deleterious role, depending on their activation dynamics from the first days after infection, which in turn depends on the infectious dose of virus received or the initial efficacy of viral control.

Preliminary results suggest that the response of animals to IFN-I is protective, with respect to both the control of viral replication and the development of disease. However, these results need to be confirmed.

Experiments are underway to refine the analysis of the role of IFN-I and to determine the role of pDCs.

None yet

In order to understand what causes severe cases of Covid19, and therefore to improve their medical management, it is essential to better understand the natural history of this disease caused by the SARS-CoV2 coronavirus. Specifically, we propose to solve the puzzle of the much debated role of type I interferons (IFN-I) and of their major cellular source during many viral infections, namely plasmacytoid dendritic cells (pDCs). We will take advantage of mutant mouse models that can be infected with Covid-Cov2 SARS, develop a disease very similar to Covid19, and have been modified for tracing or inactivating pDCs in vivo and for following IFN-I-producing cells with a high degree of resolution. This approach will allow us testing the hypothesis that IFN-I and pDCs play either beneficial or deleterious roles, depending on their activation dynamics in the first days following infection; this activation dynamics being itself dependent on the infectious dose of the virus received or on the initial efficacy of viral control.

Project coordination

Marc DALOD (Centre d'immunologie de Marseille-Luminy)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CIML Centre d'immunologie de Marseille-Luminy
CIPHE Centre d'immunophénomique

Help of the ANR 155,555 euros
Beginning and duration of the scientific project: February 2021 - 12 Months

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