Search

Background:Pneumonic plague is a fatal respiratory disease caused by Yersinia pestis. Time-course transcriptome analysis on the mechanism of pneumonic plague biphasic syndrome is lacking in the literature. Materials & methods:This study documented the disease course through bacterial load, histopathology, cytokine levels and flow cytometry. RNA-sequencing technology was used to investigate the global transcriptome profile of lung tissue in mice infected with Y. pestis. Results:Inflammation-related genes were significantly upregulated at 48 h post-infection, while genes related to cell adhesion and cytoskeletal structure were downregulated. Conclusion:NOD-like receptor and TNF signaling pathways play a plausible role in pneumonic plague biphasic syndrome and lung injury by controlling the activation and inhibition of the NF-κB signaling pathway.

This study presents a comprehensive cellular atlas describing the ongoing pulmonary immune responses in the early stages of diffuse alveolar damage. This work indicates a vital role of the hyper‐inflammatory fibroblast subset around the bronchus, in mediating neutrophil infiltration through secreting soluble signaling mediators, thus boosting neutrophilic airway inflammation.

Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single‐cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD‐induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper‐inflammatory state, and the subsequent occurrence of a CXCL1‐CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close‐knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper‐inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression. Diffuse alveolar damage (DAD) triggers intense neutrophilic airway inflammation. This work demonstrates that proinflammatory activated fibroblasts (AFib) are induced in a mouse model of DAD. Neutrophil infiltration into the airway crucially depends on their cross‐talk with AFib via the soluble CXCL1‐CXCR2 chemokine axis.