Title: TNF-α and Th17 collaborate to induce airway neutrophilia during persistent fungal infection in a MyD88 and Dectin-1-dependent fashion (40.23)
Abstract:Abstract Aspergillus fumigatus is a fungus that induces allergic bronchopulmonary aspergillosis (ABPA), a disease exhibiting both airway eosinophilia and neutrophilia. The disease is acquired through ...Abstract Aspergillus fumigatus is a fungus that induces allergic bronchopulmonary aspergillosis (ABPA), a disease exhibiting both airway eosinophilia and neutrophilia. The disease is acquired through the inhalation of spores, which are cleared efficiently in healthy humans but not in patients with cystic fibrosis or asthma. The impaired clearance and sustained inflammation contribute to the pathogenesis of ABPA. Neutrophils are important in host defense, but uncontrolled neutrophilia causes lung pathology in ABPA. We have developed an animal model of ABPA that mimics persistent fungal stimulation in ABPA. Interestingly, the model produced different outcomes in BALB/c and C57BL/6 mice with high neutrophilia in the former but low neutrophilia and high eosinophilia in the latter, which provided us with an opportunity to study the mechanisms underlying excessive airway neutrophilia. Our results show that IL-17A, which has been associated with neutrophilia in many models, was induced at similar levels in both strains. However, the BALB/c mice expressed high levels of TNF-α and collaboration between IL-17A and TNF-α was essential in inducing the high neutrophilia in BALB/c mice. Our investigations in MyD88-/- and Dectin-1-/- mice show an important contribution of both pathways in inducing high TNF-α and IL-17A responses in BALB/c mice. Taken together, we identify a novel mechanism involving the cooperation of TNF-α and Th17 for the regulation of airway neutrophilia in Aspergillus infection.Read More
Publication Year: 2010
Publication Date: 2010-04-01
Language: en
Type: article
Indexed In: ['crossref']
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot