Autoantibody of Interleukin-17A Induced by Recombinant Mycobacterium Smegmatis Attenuates Airway Inflammation in Neutrophilic Asthma

Abstract Asthma is a chronic inflammatory disorder, previous studies have shown Interleukin (IL)-17A is an important contributor to the development of severe asthma characterized by intense neutrophilic inflammation and less responsive to corticosteroid. Hence, IL-17A-neutrophil axis may be a potential therapeutic target for asthma. In our previous work, we constructed a recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS) and confirmed that it could induce the production of IL-17A autoantibody in vivo. Here, in the present study, we aim to further investigate the effects of the rMS on airway inflammation and explore the underlying mechanisms in a murine model of neutrophilic asthma. The murine model of neutrophilic asthma was established with ovalbumin (OVA), and mice were intranasally vaccinated with rMS, then IL-17A autoantibody in sera was detected, and its anti-inflammatory effects on inflammatory cell infiltration and expression of inflammatory mediators involved in IL-17A-neutrophil axis in bronchoalveolar lavage fluid (BALF) as well as histopathological changes of lung tissues were evaluated. The data showed that sustained high-titer of IL-17A autoantibody was detected in rMS group, intranasal vaccination significantly decreased inflammatory cells, cytokines and chemokines related to IL-17A-neutrophil axis in BALF, suppressed the activity of neutrophil enzyme, and histological analysis manifested the rMS remarkably reduced inflammatory cell infiltration, mucus secretion and airway epithelial thickness. Overall, these results demonstrate the rMS ameliorated airway inflammation in mice with neutrophilic asthma via inducing IL-17A autoantibody and regulating the IL-17A-neutrophil axis, thus providing a possible novel treatment in neutrophilic asthma.