Lung epithelial cell–derived C3 protects against pneumonia-induced lung injury

• DOI: 10.1126/sciimmunol.abp9547
• Publication Date: 2023-02-03T18:58:23Z
• Authors: Sanjaya K. Sahu; Ayşe N. Ozantürk; Devesha H. Kulkarni; Lina Ma; Ruteja A. Barve; Linus Dannull; Angel Lu; Marick Starick; Ja’Nia McPhatter; Lorena Garnica; Maxwell Sanfillip...; Jeremy Kunen; Xiaobo Wu; Andrew E. Gelman; Steven L. Brody; John P. Atkinson; Hrishikesh S. Kul...
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; Pneumonia, Bacterial; Humans; Animals; Epithelial Cells; Lung Injury; Lung; 3. Good health; Complement Factor B

The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated critical importance of tissue-specific expression in cell survival. Here, we analyzed effects local versus peripheral sources model acute bacterial pneumonia induced Pseudomonas aeruginosa . Whereas mice with global deficiency had severe pneumonia-induced lung injury, those deficient only liver-derived remained protected, comparable to wild-type mice. Human transcriptome analysis showed that secretory epithelial cells, such as club express high levels mRNA. Mice tamoxifen-induced gene ablation from cells worse pulmonary injury compared similarly treated controls, despite maintaining normal circulating levels. Last, both mouse and cultured primary human airway stress-induced death associated parallels seen Factor B rather than C3a receptor deficiency. Moreover, C3-mediated reduction requires alternative pathway B. Thus, our findings suggest reliant on locally derived protects mucosal barrier.