Molecular Immunopathogenesis of Dermatophagoides Pteronyssinus (Der P1) Allergen on the Progression of Pulmonary Toxocariasis-Causing Asthma and Fibrosis by Proteomic Approaches

Asthma is a common chronic tracheal inflammatory disease with pathological characteristics of airway hyperresponsiveness and airway remodeling; idiopathic pulmonary fibrosis (IPF) is an unknown etiological cause with pathological characteristics of alveolar structural disorder that can lead to death due to lung function deterioration. Toxocara canis transmitted by dogs may infect humans and larval invasion of the lungs can cause pulmonary toxocariasis (PT) via blood circulation, but the patients did not show significant clinical symptoms due to latent infection. Experiments indicate that Toxocara infection mainly caused Th2 cell immune-based lesions, it is still unclear as whether PT may cause asthma or PF and if exposed to dust mite allergens will worsen the development of these symptoms also remains unknown. The preliminary results of the applicant are indicated as follows: (1). A murine model of PT has been established well. The larvae invading the lungs can be divided into three stages including the initial stage (within 1 week), middle stage (4-12 weeks) and late stage (16-28 weeks) (Vet Parasitol, 2003 and Taiwan Vet J, 2004); (2) Inflammation and fibrosis-related proteins TGF-β1, S100A12 and PCNA can be detected in the PT lung tissue. This three-year project intends to explore the molecular mechanisms underlying the development of the PT-causing asthma and PF disease or if exposure to allergens derived from Dermatophagoides pteronyssinus may worsen these diseases progression will be assessed by proteomics approaches. Year 1: Asthma severity from mice with pulmonary toxocariasis caused by high dose of 1000 T. canis ova, moderate dose of 100 T. canis ova or light dose of 10 T. canis ova will be sacrificed on day 2 (early stage), week 8 (middle stage), or week 16 (late stage) that will be compared with that from mice induced by OVA. Year 2: Pulmonary fibrosis severity from mice with pulmonary toxocariasis caused by high dose of 1000 T. canis ova, moderate dose of 100 T. canis ova or light dose of 10 T. canis ova will be sacrificed on day 2 (early stage), week 8 (middle stage), or week 16 (late stage) that will be compared with that from mice treated by Bleomycin. Year 3: Select the group of mice with the most severe and mildest asthma and PF symptoms in the first and second years of the trial, then sensitized with the Dermatophagoides pteronyssinus Der p 1 to evaluate the exacerbation degree of asthma or PF progression.