CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection.

Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells.

Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease.

While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model.

Gpnmb and Spp1 mark a conserved macrophage injury response masking fibrosis-specific programming in the lung.

Macrophages are required for healthy repair of the lungs following injury, but they are also implicated in driving dysregulated repair with fibrosis. How these 2 distinct outcomes of lung injury are mediated by different macrophage subsets is unknown. To assess this, single-cell RNA-Seq was performed on lung macrophages isolated from mice treated with LPS or bleomycin.

Requirement for Fucosyltransferase 2 in Allergic Airway Hyperreactivity and Mucus Obstruction.

Mucus hypersecretion is an important pathological problem in respiratory diseases. Mucus accumulates in the airways of people with asthma, and it contributes to airflow limitation by forming plugs that occlude airways. Current treatments have minimal effects on mucus or its chief components, the polymeric mucin glycoproteins MUC5AC and MUC5B.