Theranostics 2022; 12(11):5125-5137. doi:10.7150/thno.74809 This issue Cite

Research Paper

Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae

Shengsen Chen1,2*, Xinyun Zhang2,3*, Cheng Yang2,4, Shi Wang1✉, Hao Shen2✉

1. Department of Endoscopy (the bronchoscope group), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
2. Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia 19104, USA.
3. Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
4. Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
*These authors are contributed equally to this work.

Citation:
Chen S, Zhang X, Yang C, Wang S, Shen H. Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae. Theranostics 2022; 12(11):5125-5137. doi:10.7150/thno.74809. https://www.thno.org/v12p5125.htm
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Abstract

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Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) has a poor prognosis and lacks effective therapy. Animal models that mimic AE-IPF can greatly accelerate investigation of its pathogenesis and development of effective therapy. However, there are few reports of animal models of AE-IPF caused by bacteria. Thus, our study aimed to establish a mouse model of bacterium‐induced AE‐IPF and explore the potential pathogenic mechanism of AE‐IPF.

Methods: Mice were instilled intranasally with bleomycin (BLM) followed by non-typeable Haemophilus influenzae (NTHi) strain NT127. Murine survival, bacterial load, body weight and pulmonary histopathological changes were evaluated. We analyzed the T cell and inflammatory cell responses in the lungs.

Results: Infection with 107 CFU NT127 triggered AE in mice with PF induced by 30 μg BLM. Compared with BLM-instilled mice, the BLM/NT127-treated mice showed more obvious airway inflammation, lower survival rate, higher inflammatory cell response, and increased proportions and numbers of IL-17+CD4+, IL-17+ γδ T, IL-22+CD4+ and regulatory T (Treg) cells in lungs. γδ T cells were the predominant source of IL-17. IL-17 gene knockout mice with AE-IPF had quicker body weight recovery, milder pulmonary inflammation and fibrosis, stronger IL-22+CD4+T, TGF-β+ γδ T and Treg cell responses, and weaker neutrophil and eosinophil responses than wild-type mice with AE-IPF.

Conclusions: NTHi infection after BLM-induced IPF can cause AE‐IPF in a murine model. This novel model can be used to investigate the pathogenesis of AE‐IPF and develop new therapies for AE‐IPF caused by bacteria. IL-17 is essential for the development of AE-IPF, and it may be a new therapeutic target for bacteria-induced AE-IPF.

Keywords: idiopathic pulmonary fibrosis, acute exacerbations, nontypeable Haemophilus influenzae, IL-17, γδ T cell


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APA
Chen, S., Zhang, X., Yang, C., Wang, S., Shen, H. (2022). Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae. Theranostics, 12(11), 5125-5137. https://doi.org/10.7150/thno.74809.

ACS
Chen, S.; Zhang, X.; Yang, C.; Wang, S.; Shen, H. Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae. Theranostics 2022, 12 (11), 5125-5137. DOI: 10.7150/thno.74809.

NLM
Chen S, Zhang X, Yang C, Wang S, Shen H. Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae. Theranostics 2022; 12(11):5125-5137. doi:10.7150/thno.74809. https://www.thno.org/v12p5125.htm

CSE
Chen S, Zhang X, Yang C, Wang S, Shen H. 2022. Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae. Theranostics. 12(11):5125-5137.

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