title: Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.
abstract: Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation.
authors.affiliation: Department of Paediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Wanting
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Paediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Shanghai Jiao Tong University Affiliated Children's Hospital, Shanghai, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Paediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Liangxia
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Paediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D007249:Inflammation / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000276:immunology*; D011014:Pneumonia / Q000150:complications / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011995:Recombination, Genetic / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D020381:Interleukin-17; D012333:RNA, Messenger