Biology subjects

Boisseau, C.

Publications and source records attributed to Boisseau, C..

3 recordsLinked to original sources

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↗

bioRxiv2022

Mucosal administration of anti-bacterial antibody provides long-term cross-protection against Pseudomonas aeruginosa respiratory infection

Bacterial respiratory infections, associated with acute, sometimes recurrent infections and with chronic respiratory diseases, are a major threat for human health. Mucosal administration of therapeutic antibodies (Ab), using the airways as a delivery route, has a tremendous opportunity to benefit to patients with respiratory infections, with remarkable preclinical achievements in both viral and bacterial respiratory infection models and ongoing clinical developments. The primary mode of action of anti-infective Ab delivered through the airways is pathogen neutralization and to a lesser extent, Fc-mediated direct recruitment of immune effectors to facilitate their elimination. Using a mouse model of acute pneumonia induced by P. aeruginosa, a bacterium frequently associated with multidrug resistance and a high rate of recurrence, we characterized an immunomodulatory mode of action of anti-bacterial Ab. Beyond the rapid and efficient containment of the primary infection, the anti-infective Ab delivered through the airways harnessed adaptive immunity to provide a long-term response, preventing from a secondary pathogen infection. This effect is specific and dependent on the Ab dose, intensity of infection and antigen expression by the pathogen upon primary infection. As shown by adoptive transfer experiments, it is mediated by a sustained and protective humoral immune response. Interestingly, the long-lasting response protected partially against secondary infections due to heterologous P. aeruginosa strains. Overall, our findings suggest that mucosal delivery of Ab through the airways offers a dual advantage: a rapid onset of action to neutralize respiratory bacteria and a long-term protection against secondary infections, thereby opening novel perspectives for the development of anti-infective antibody delivered to the lung mucosa, to treat respiratory infections.

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↗