IL-17 Aggravates Pseudomonas aeruginosa Airway Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

• Published in: Frontiers in immunology 2022-01, Vol.12, p.811803-811803
• Main Authors: Ding, Fengming, Han, Lei, Fu, Qiang, Fan, Xinxin, Tang, Rong, Lv, Chengjian, Xue, Yishu, Tian, Xue, Zhang, Min
• Format: Article
• Language: English
• Subjects: Animals; Autoantibodies - immunology; Bacterial Load; Biomarkers; COPD; cytokine profile; Cytokines - metabolism; Disease Models, Animal; Disease Progression; Female; Host-Pathogen Interactions; Humans; IL-17; Immunology; Inflammation Mediators - metabolism; Interleukin-17 - immunology; Interleukin-17 - metabolism; lung function; Male; Mice; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - complications; Pseudomonas Infections - metabolism; Pseudomonas Infections - microbiology; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - diagnosis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.811803

airway infection increases risks of exacerbations and mortality in chronic obstructive pulmonary disease (COPD). We aimed to elucidate the role of IL-17 in the pathogenesis. We examined the expression and influences of IL-23/IL-17A in patients with stable COPD ( = 33) or acute COPD exacerbations with infection ( = 34). A mouse model of COPD (C57BL/6) was used to investigate the role of IL-17A in host inflammatory responses against infection through the application of IL-17A-neutralizing antibody or recombinant IL-17A. We found that infection increased IL-23/17A signaling in lungs of both COPD patients and COPD mouse models. When COPD mouse models were treated with neutralizing antibody targeting IL-17A, induced a significantly less polymorphonuclear leukocyte infiltration and less bacterial burden in their lungs compared to those of untreated counterparts. The lung function was also improved by neutralizing antibody. Furthermore, IL-17A-signaling blockade significantly reduced the expression of pro-inflammatory cytokine IL-1β, IL-18, TNF-α, CXCL1, CXCL15 and MMP-9, and increased the expression of anti-inflammatory cytokine IL-10 and IL-1Ra. The application of mouse recombinant IL-17A exacerbated -mediated inflammatory responses and pulmonary dysfunction in COPD mouse models. A cytokine protein array revealed that the expression of retinol binding protein 4 (RBP4) was down-regulated by IL-17A, and exogenous RBP4-recombinant protein resulted in a decrease in the severity of induced airway dysfunction. Concurrent application of IL-17A-neutralizing antibody and ciprofloxacin attenuated airway inflammation and ventilation after inoculation of in COPD mouse models. Our results revealed that IL-17 plays a detrimental role in the pathogenesis of airway infection during acute exacerbations of COPD. Targeting IL-17A is a potential therapeutic strategy in controlling the outcomes of infection in COPD patients.