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Function of interferons in murine pulmonary PCM: comparative evaluation of disease severity between control mice and knockouts for IFN-alpha/betaR, IFN-gammaR and IRF-1

Grant number: 17/01794-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2017
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Flávio Vieira Loures
Grantee:Bruno Borges da Silva
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/04783-2 - Study of the plasmacytoid and myeloid dendritic cells function during Paracoccidioides brasiliensis infection, AP.JP

Abstract

Dendritic cells (DCs) constitute a link between the innate and adaptive immunity. According to the subclass and activation pattern they may play an important role in regulatory and protective immunological effects to the host. In paracoccidioidomycosis (PCM), the systemic mycosis with highest incidence in Latin America, the role of DCs has been poorly studied, although several lines of work have characterized the main parameters of the adaptive immune response in mild and severe forms of the disease. A previous study has demonstrated that the resistance and susceptibility to Paracoccidioides brasiliensis were associated with different DC subpopulations. In addition, in a work at the University of Massachusetts I could demonstrate that plasmacytoid DCs (pDCs), originally described as the main regulators of viral infections, and developed an effective growth control of Aspergillus fumigatus hyphae. Besides, pDCs were able to externalize their DNA forming extracellular traps-like structures when in contact with the fungus. These data warrant further studies that may increase our understanding about the DCs (myeloid and plasmacytoid) function in human and murine pulmonary PCM. We intend to study the phagocytic and fungicide activity, the cytokine production and antigen-presenting function of DCs against P. brasiliensis. The study will be carried out with cells from healthy donors, as well as cells derived from patients suffering from the adult form of the disease. As a complementary study, experiments will be performed in mice to better understand the role of type I IFN in PCM. Thus, we are going to study several parameters of the immune response of C57BL/6 IFN-abR -deficient and C57BL/6 WT P. brasiliensis infected mice. (AU)