GUT-MBC · Memory B cell dynamics in the gut mucosa
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-08-01 → 2024-07-31
- EU contribution
- €184,708
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Memory B cell dynamics in the gut mucosa
The immune system has the ability to respond quickly when it encounters a pathogen for the second time thanks to the generation of long-lasting memory cells from B and T lymphocytes. Humoral immunity in particular depends on two main types of B cells: long-lived plasma cells (LLPCs) that produce antibodies, and memory B cells (MBCs), which remain inactive until they encounter the same pathogen again when they quickly produce antibodies. These memory B cells have been extensively studied in primary and secondary lymphoid organs but recently, there has been more focus on how they work in barrier tissues like the lungs and intestines. Recently, our research group found that after flu infection, more than 75% of B cells generated in the lungs became MBCs situated in specific areas near the bronchi to give a rapid protection against future infections in the airways. However, it is still unclear if this also happens in the intestines. In our current study, we are examining how long-term immunity develops in the intestines after an infection with Salmonella typhimurium. Unlike what we observed in the lungs, nearly 90% of these B cells in the intestines become LLPCs, while only about 10% become MBCs. This suggests that while long-term immune response in the lungs relies mainly on MBCs, in the intestines it is primarily driven by LLPCs. We aim to find out whether these different strategies are due to the type of pathogen, the environment of the tissue, or a combination of both. Understanding these two different memory strategies could give us the clues to effectively design and develop nasal and oral vaccines against mucosal pathogens.
Data: CORDIS, © European Union
Project objective
Salmonellosis is one of the most common and widespread food-borne diseases worldwide. This disease, caused by the gram-negative bacteria Salmonella, affects millions of people every year, leading to more than one hundred thousand deaths around the world. Currently, there is no licensed vaccine against Salmonella to face out this health issue.At present, most licensed human vaccines rely on the induction of long-lived memory lymphocytes. Memory B cells are a key part of this strategy, as they can rapidly differentiate into antibody-secreting cells and neutralize pathogens in case of future exposures. Despite their protective role, we have very limited knowledge on the dynamics of memory B cells in the context of gastrointestinal infection.GUT-MBC aims to unravel the developmental kinetics, spatial distribution and tissue diversity of memory B cells in the gastrointestinal tract upon Salmonella infection. To achieve this goal, I will take advantage of a transgenic mouse line to track memory B cells in vivo, gastrointestinal infection models, multiparametric flow cytometry, cutting edge imaging techniques and single-cell RNA-seq. Understanding how memory B cells are generated and maintained in the gut mucosa and associated lymphoid tissues upon infection is critical for the future design of protective vaccines against Salmonella and other emerging enteric pathogens.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union