tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol
. 2025 Oct 10.
doi: 10.1165/rcmb.2024-0405OC. Online ahead of print. Integrated Longitudinal Transcriptomic and Proteomic Analysis of the Murine Lung Response to Influenza A Virus
Tim Flerlage[SUP] 1 [/SUP], David F Boyd[SUP] 2 [/SUP], Brandi Clark[SUP] 3 [/SUP], Nikhil G Marudai[SUP] 4 [/SUP], Shally Saini[SUP] 4 [/SUP], Cliff Guy[SUP] 3 [/SUP], Kristine Pobre-Piza[SUP] 5 [/SUP], Jeremy Chase Crawford[SUP] 6 [/SUP], Suresh Poudel[SUP] 3 [/SUP], Anthony A High[SUP] 7 [/SUP], Suiping Zhou[SUP] 7 [/SUP], Xusheng Wang[SUP] 7 [/SUP], Sherri Surman[SUP] 8 [/SUP], Bart Jones[SUP] 8 [/SUP], Charles W Frevert[SUP] 9 [/SUP], Paul G Thomas[SUP] 6 [/SUP]
Affiliations
Lung injury caused by influenza is a leading cause of respiratory infection-related morbidity and mortality worldwide. In its severe form, influenza can cause acute respiratory distress syndrome (ARDS), which manifests as severe hypoxemic respiratory failure. Survivors of the acute stage of ARDS may develop lung fibrosis. The mechanisms underlying fibrotic responses in this context are unknown. In this study, we investigate fibroblast responses to influenza challenge using single cell gene expression (scGEX) and two-dimensional liquid chromatography coupled with tandem/mass spectrometry (TMT-LC/LC-MS/MS) on lung tissue collected longitudinally in a murine model of influenza A virus (IAV) infection. By TMT-LC/LC-MS/MS, we identified profound changes in the composition of the lung matrisome, which were most evident 10 days after infection. In this context, we identified transcriptional heterogeneity amongst proximal/adventitial fibroblasts expressing Pi16 and Col15a1 as well as a myofibroblast activation state characterized by expression of Tnc, Spp1, Grem1, and Cthrc1. This activation state was transcriptionally similar to those previously described in other contexts. Together, these data suggest compartmentalization and conservation of pulmonary fibroblast responses to lung injury of different primary etiologies.
Keywords: ARDS; Influenza; fibrosis.
. 2025 Oct 10.
doi: 10.1165/rcmb.2024-0405OC. Online ahead of print. Integrated Longitudinal Transcriptomic and Proteomic Analysis of the Murine Lung Response to Influenza A Virus
Tim Flerlage[SUP] 1 [/SUP], David F Boyd[SUP] 2 [/SUP], Brandi Clark[SUP] 3 [/SUP], Nikhil G Marudai[SUP] 4 [/SUP], Shally Saini[SUP] 4 [/SUP], Cliff Guy[SUP] 3 [/SUP], Kristine Pobre-Piza[SUP] 5 [/SUP], Jeremy Chase Crawford[SUP] 6 [/SUP], Suresh Poudel[SUP] 3 [/SUP], Anthony A High[SUP] 7 [/SUP], Suiping Zhou[SUP] 7 [/SUP], Xusheng Wang[SUP] 7 [/SUP], Sherri Surman[SUP] 8 [/SUP], Bart Jones[SUP] 8 [/SUP], Charles W Frevert[SUP] 9 [/SUP], Paul G Thomas[SUP] 6 [/SUP]
Affiliations
- PMID: 41072037
- DOI: 10.1165/rcmb.2024-0405OC
Lung injury caused by influenza is a leading cause of respiratory infection-related morbidity and mortality worldwide. In its severe form, influenza can cause acute respiratory distress syndrome (ARDS), which manifests as severe hypoxemic respiratory failure. Survivors of the acute stage of ARDS may develop lung fibrosis. The mechanisms underlying fibrotic responses in this context are unknown. In this study, we investigate fibroblast responses to influenza challenge using single cell gene expression (scGEX) and two-dimensional liquid chromatography coupled with tandem/mass spectrometry (TMT-LC/LC-MS/MS) on lung tissue collected longitudinally in a murine model of influenza A virus (IAV) infection. By TMT-LC/LC-MS/MS, we identified profound changes in the composition of the lung matrisome, which were most evident 10 days after infection. In this context, we identified transcriptional heterogeneity amongst proximal/adventitial fibroblasts expressing Pi16 and Col15a1 as well as a myofibroblast activation state characterized by expression of Tnc, Spp1, Grem1, and Cthrc1. This activation state was transcriptionally similar to those previously described in other contexts. Together, these data suggest compartmentalization and conservation of pulmonary fibroblast responses to lung injury of different primary etiologies.
Keywords: ARDS; Influenza; fibrosis.