Biology subjects

Jouan, Y.

Publications and source records attributed to Jouan, Y..

3 recordsLinked to original sources

bioRxiv2025

MAIT cells protect in severe pneumococcal pneumonia by regulating neutrophil/macrophage antimicrobial activities

Mucosal-Associated Invariant T (MAIT) cells populate the lung tissue where they contribute to defense against respiratory infections. While MAIT cells have been implicated in host resistance to infections caused by Gram-negative bacteria, their contribution in immunity against Gram-positive bacteria-driven pneumonia is still enigmatic. Here, we demonstrate that both mouse and human MAIT cells are activated during severe infection caused by Streptococcus pneumoniae, the major cause of community-acquired bacterial pneumonia. Upon infection, lung MAIT cells undergo a transcriptional reprogramming associated with acquisition of potent antimicrobial properties. MAIT cell-deficient mice are more susceptible to pneumococcal pneumonia, including higher mortality, uncontrolled bacterial growth and dissemination, and impaired neutrophil and interstitial macrophage activity. Moreover, prophylactic stimulation of MAIT cells using cognate antigen protects from pneumococcus-induced lethal pneumonia. These findings demonstrate that MAIT cells are key cellular actors during Gram-positive bacterial infections.

immunology↗

bioRxiv2023

IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections

Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of Programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1+ neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1- counterpart. VRI-induced regulatory PD-L1+ neutrophils were generated in the bone marrow in an IFN-{gamma}-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation and reduced expression of resolving factors. These findings suggest that PD-L1+ neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.

immunology↗

bioRxiv2020

High dimensional single-cell analysis reveals iNKT cell developmental trajectories and effector fate decision

CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that give rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomic analysis combined with functional assays, we revealed an unappreciated diversity among thymic iNKT cells, especially among iNKT1 cells. Mathematical modelling and biological methods unravelled a developmental map whereby iNKT2 cells constitute a transient branching point towards the generation of iNKT1 and iNKT17 cells, which reconciles the two previously proposed models. In addition, we identified the transcription co-factor Four-and-a-half LIM domains protein 2 (FHL2) as a critical cell-intrinsic regulator of iNKT1 specification. Thus, these data illustrate the changing transcriptional network that guides iNKT cell effector fate.

immunology↗