Recruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury.

The lung is constantly exposed to airborne pathogens and particles that can cause alveolar damage. Hence, appropriate repair responses are essential for gas exchange and life. Here, we deciphered the spatiotemporal trajectory and function of an atypical population of macrophages after lung injury. Post-influenza A virus (IAV) infection, short-lived monocyte-derived Ly6G-expressing macrophages (Ly6G+ Macs) were recruited to the alveoli of lung perilesional areas. Ly6G+ Macs engulfed immune cells, exhibited a high metabolic potential, and clustered with alveolar type 2 epithelial cells (AT2s) in zones of active epithelial regeneration. Ly6G+ Macs were partially dependent on granulocyte-macrophage colony-stimulating factor and interleukin-4 receptor signaling and were essential for AT2-dependent alveolar regeneration. Similar macrophages were recruited in other models of injury and in the airspaces of lungs from patients with suspected pneumonia. This study identifies perilesional alveolar Ly6G+ Macs as a spatially restricted, short-lived macrophage subset promoting epithelial regeneration postinjury, thus representing an attractive therapeutic target for treating lung damage.

Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity.

Asthma encompasses a spectrum of heterogenous immune-mediated respiratory disorders sharing a similar clinical pattern characterized by cough, wheeze and exercise intolerance. In horses, equine asthma can be subdivided into severe or moderate asthma according to clinical symptoms and the extent of airway neutrophilic inflammation. While severe asthmatic horses are characterized by an elevated neutrophilic inflammation of the lower airways, cough, dyspnea at rest and high mucus secretion, horses with moderate asthma show a milder neutrophilic inflammation, exhibit intolerance to exercise but no labored breathing at rest. Yet, the physiopathology of different phenotypes of equine asthma remains poorly understood and there is a need to elucidate the underlying mechanisms tailoring those phenotypes in order to improve clinical management and elaborate novel therapeutic strategies. In this study, we sought to quantify the presence of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluids (BALF) of moderate or severe asthmatic horses and healthy controls, and assessed whether NETs correlated with disease severity. To this end, we evaluated the amounts of NETs by measuring cell-free DNA and MPO-DNA complexes in BALF supernatants or by quantifying NETs release by BALF cells by confocal microscopy. We were able to unequivocally identify elevated NETs levels in BALF of severe asthmatic horses as compared to healthy controls or moderate asthmatic horses. Moreover, we provided evidence that BALF NETs release was a specific feature seen in severe equine asthma, as opposed to moderate asthma, and correlated with disease severity. Finally, we showed that NETs could act as a predictive factor for severe equine asthma. Our study thus uniquely identifies NETs in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms. Our data also suggest that NETs represent a relevant biomarker, a putative driver and a potential therapeutic target in severe asthma disease.