Role of dendritic cell subsets and TLR9 in the exacerbation of allergic asthma during ongoing pneumococcal pneumonia

• Grant number: 15/20799-9
• Support Opportunities: Scholarships abroad - Research
• Start date: March 15, 2016
• End date: March 14, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Vânia Luiza Deperon Bonato
• Host Investigator: Tim Sparwasser
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: TWINCORE Center for Experimental and Clinical Infection Research, Germany

Abstract

Asthma is a complex and heterogeneous disease. While allergic asthma, generally defined as mild asthma, is characterized by IgE production, Th2 cell activation and eosinophil recruitment, non-allergic asthma, defined as moderate-severe asthma, is characterized by Th17 cell activation and mixed recruitment of eosinophils and neutrophils. Viruses, bacterial infections and pollutants are factors associated with severity of asthma. The aim of this project is to test the hypothesis that infection by Streptococcus pneumoniae exacerbates the allergic inflammation and to study the mechanism involved in the exacerbation. Our hypothesis is based on the premise that the bacterial infection changes the phenotype of allergic asthma (Th2) for non-allergic (non Th2) asthma, and dendritic cells and epithelial cells play a central role in this process. Dendritic cells are key regulators both in the generation and in the perpetuation of allergic airway responses. Allergen-activated epithelial cells secrete different mediators which induce Th2 cell differentiation. In addition, dendritic cells and epithelial cells participate actively in the immune response against S. pneumoniae. Using an experimental asthma model induced by allergen exposure followed by S. pneumoniae infection, we will quantify and evaluate the function of myeloid and plasmacytoid dendritic cells in the allergic asthma exacerbation. To confirm the role of dendritic cells in the asthma exacerbation, different experimental approaches employing depletion of CD11c+ cells, conditional TLR9-/- dendritic cell mice and plasmacytoid dendritic cell transfer will be performed. The comprehension of the processes which orchestrate different patterns of inflammation in the allergic or non-allergic asthma could drive the development of individualized therapies directed not only to treat symptoms, but to cure the disease. (AU)