The opportunistic fungal pathogen Aspergillus fumigatus is the causative agent of more than 90% of all Invasive Aspergillosis (IA) infections diagnosed in immunosuppressed patients. Exposure to A. fumigatus can also lead to the development of allergic asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in patients with atopic asthma or Cystic Fibrosis. Fungus-specific CD4 T cell responses are important in defense against invasive disease and mediate the development of allergic responses. Thus, understanding the factors that control the expansion and formation of fungus-specific memory CD4 T cells will lay the foundation for the future development of novel immune-based therapeutic strategies to enhance or inhibit fungus-specific immunity. In this proposal, the applicant will examine the contributions of regulatory T cells (Tregs), T cell- intrinsic inhibitor receptors (PD-1 and CTLA-4) and CCR2+ dendritic cells (CCR2+DCs) to the formation of memory CD4 T cells in the context of a pulmonary infection with A. fumigatus and in the development of fungal allergic asthma. The applicant will be supported by a comprehensive training plan to promote her career development as an independent scientist and to help her attain a PhD degree. The long-term goal of the applicant is to become a successful, well-funded, independent researcher. As a woman of Hispanic descent the applicant is committed to contributing to the future development of research programs to address health disparities and diversity in biomedical science's workforce.
The opportunistic fungal pathogen Aspergillus fumigatus is the most common causative agent of invasive aspergillosis and can also trigger the development of allergic asthma responses. Immune responses to this fungus are central in the pathogenesis of fungal allergic asthma and in the prevention of invasive fungal disease. The studies proposed in this application will elucidate the specific contributions of immune regulatory mechanisms that promote the proper eradication of A. fumigatus while preventing excessive tissue damage to the host. The characterization of relevant immune regulatory mechanisms will facilitate the development of novel immune based therapeutic interventions for the treatment of invasive fungal disease and allergic asthma.
|Espinosa, Vanessa; Jhingran, Anupam; Dutta, Orchi et al. (2014) Inflammatory monocytes orchestrate innate antifungal immunity in the lung. PLoS Pathog 10:e1003940|