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Type I interferons function in murine pulmonary PCM: comparative assessment of disease severity between control and knockout mice for IFN-aBR

Grant number: 15/12328-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2015
Effective date (End): October 31, 2016
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Flávio Vieira Loures
Grantee:Daniella Helena Medeiros
Host 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


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 pDCs and type I IFN in PCM. Thus, we are going to study several parameters of the immune response of C57BL/6 IFN-±²R -deficient mice and C57BL/6 WT mice depleted of pDCs compared to their normal controls.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE ARAUJO, ELISEU FRANK; MEDEIROS, DANIELLA HELENA; DE LIMA GALDINO, NAYANE ALVES; CONDINO-NETO, ANTONIO; GARCIA CALICH, VERA LUCIA; LOURES, FLAVIO VIEIRA. Tolerogenic Plasmacytoid Dendritic Cells Control Paracoccidioides brasiliensis Infection by Inducting Regulatory T Cells in an IDO-Dependent Manner. PLOS PATHOGENS, v. 12, n. 12, . (14/18668-0, 15/12328-6, 14/22630-9)

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