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Study of the plasmacytoid and myeloid dendritic cells function during Paracoccidioides brasiliensis infection

Grant number: 14/04783-2
Support type:Research Grants - Young Investigators Grants
Duration: November 01, 2014 - October 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Flávio Vieira Loures
Grantee:Flávio Vieira Loures
Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
Assoc. researchers:Antonio Condino Neto ; Vera Lucia Garcia Calich
Associated grant(s):18/14762-3 - Immunosuppression in paracoccidioidomycosis: the regulatory role of myeloid-derived suppressor cells (MDSCs) on host immunity, tissue pathology and genetic adaptation of fungal cells, AP.JP2
17/14602-3 - The IDO-AhR axis controls Th17/Treg immunity in a pulmonary model of fungal infection, PUB.ART
Associated scholarship(s):17/00711-5 - Characterization of human pDCs in PCM: innate receptors expression and tolerance mechanisms, BP.IC
17/01794-1 - 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, BP.IC
15/12328-6 - Type I interferons function in murine pulmonary PCM: comparative assessment of disease severity between control and knockout mice for IFN-aBR, BP.IC
14/22630-9 - Study of the plasmacytoid and myeloid dendritic cells function during Paracoccidioides Brasiliensis infection, BP.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-±²R -deficient and C57BL/6 WT P. brasiliensis infected mice. (AU)

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)
PREITE, NYCOLAS WILLIAN; FERIOTTI, CLAUDIA; DE LIMA, DHEMERSON SOUZA; DA SILVA, BRUNO BORGES; CONDINO-NETO, ANTONIO; PONTILLO, ALESSANDRA; GARCIA CALICH, VERA LUCIA; LOURES, FLAVIO VIEIRA. The syk-coupled C-Type lectin receptors Dectin-2 and Dectin-3 are involved in Paracoccidioides brasiliensis recognition by human Plasmacytoid Dendritic cells. FRONTIERS IN IMMUNOLOGY, v. 9, MAR 20 2018. Web of Science Citations: 1.
NUNES, BRUNO GHIROTTO; LOURES, FLAVIO VIEIRA; SIQUEIRA BUENO, HELOISA MARIA; CANGUSSU, ERICA BARONI; GOULART, ERNESTO; COATTI, GIULIANA CASTELLO; CALDINI, ELIA GARCIA; CONDINO-NETO, ANTONIO; ZATZ, MAYANA. Immunoglobulin therapy ameliorates the phenotype and increases lifespan in the severely affected dystrophin-utrophin double knockout mice. European Journal of Human Genetics, v. 25, n. 12, p. 1388-1396, DEC 2017. Web of Science Citations: 0.
DE ARAUJO, ELISEU FRANK; FERIOTTI, CLAUDIA; DE LIMA GALDINO, NAYANE ALVES; PREITE, NYCOLAS WILLIAN; GARCIA CALICH, VERA LUCIA; LOURES, FLAVIO VIEIRA. The IDO-Ahr axis controls Th17/Treg Immunity in a Pulmonary Model of Fungal Infection. FRONTIERS IN IMMUNOLOGY, v. 8, JUL 24 2017. Web of Science Citations: 10.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.