How does plasmacytoid dendritic cells contribute to host defenses against invasive aspergillosis?

• Grant number: 12/03878-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 01, 2012
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vera Lucia Garcia Calich
• Grantee: Flávio Vieira Loures
• Supervisor: Stuart M. Levitz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Massachusetts Medical School (UMMS), United States

Abstract

In preliminary studies Ramirez-Ortiz et al. 2011, demonstrate that plasmacytoid dendritic cells (pDCs) phagocytose Aspergillus fumigatus conidia and spread over the surface of the hyphal morphotype. In response to hyphal stimulation, pDCs directly inhibit fungal growth and release IFN-± and TNF-±. These studies together with this project challenge the prevailing dogma regarding the specialized role of pDCs by demonstrating for the first time that pDCs play a non-redundant role in host defenses against a fungal pathogen. To performer this, we intend to study the role played by innate immunity receptors in the interaction between pDCs and the different A. fumigatus morphotypes. Furthermore, in vivo experiments will evaluate the effect of pDC depletion in the severity of pulmonary aspergillosis. The depletion effect on immune response against A. fumigatus will be study as well. As a complementary study we intend to investigate the kinetics of pDCs influx to the lungs, and also verified how the pDCs directly interact with the different A. fumigatus morphotypes. (AU)