期刊
MUCOSAL IMMUNOLOGY
卷 13, 期 1, 页码 128-139出版社
SPRINGERNATURE
DOI: 10.1038/s41385-019-0212-y
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资金
- Region Centre-Val de Loire under the program ARD 2020 Biomedicaments
- French Higher Education and Research ministry under the program Investissements d'avenir: LabEx MAbImprove [ANR-10-LABX-53-01]
- Inserm
- CNRS
- University of Tours
- Pasteur Institute of Lille
- AZM foundation
- Antoine RABBAT doctoral fellowship from the Fonds de Recherche en Sante Respiratoire under Fondation du Souffle
- French Institute of cancer (INCa)
Interleukin-7 (IL-7) is a critical cytokine in B- and T-lymphocyte development and maturation. Recent evidence suggests that IL-7 is a preferential homeostatic and survival factor for ROR gamma t(+) innate T cells such as natural killer T (NKT) cells, gamma delta T cells, and mucosal-associated invariant T (MAIT) cells in the periphery. Given the important contribution of these populations in antibacterial immunity at barrier sites, we questioned whether IL-7 could be instrumental in boosting the local host immune response against respiratory bacterial infection. By using a cytokine-monoclonal antibody approach, we illustrated a role for topical IL-7 delivery in increasing the pool of ROR gamma t(+) IL-17A-producing innate T cells. Prophylactic IL-7 treatment prior to Streptococcus pneumoniae infection led to better bacterial containment, a process associated with increased neutrophilia and that depended on gamma delta T cells and IL-17A. Last, combined delivery of IL-7 and alpha-galactosylceramide (alpha-GalCer), a potent agonist for invariant NKT (iNKT) cells, conferred an almost total protection in terms of survival, an effect associated with enhanced IL-17 production by innate T cells and neutrophilia. Collectively, we provide a proof of concept that IL-7 enables fine-tuning of innate T- cell functions. This might pave the way for considering IL-7 as an innovative biotherapeutic against bacterial infection.
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