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Involvement of toll-like receptor, integrins and their respective cell signaling pathways in cytokine secretion by epithelial cells during infection with Paracoccidioides brasiliensis

Grant number: 16/06285-5
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2016
Effective date (End): January 31, 2020
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Erika Suzuki de Toledo
Grantee:Bianca Carla Silva Campitelli de Barros
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):17/20214-6 - Comparative analysis of cell signaling in epithelial cells cultured as monolayer or spheroids in the presence of conditioned medium of Paracoccidioides brasiliensis, BE.EP.DR


Paracoccidioidomycosis is caused by the fungal pathogen of the genus Paracoccidioides and is the most prevalent systemic mycosis in Latin America. About 80% of the cases occur in Brazil. And, due to the increasing number of cases of this mycosis in our country, studies about interactions between these fungi and host are essential to understand the events involved in the establishment of infection and spread of pathogen.Epithelial cells are the first contact site for pathogens. Besides forming a physical barrier against particles, these cells contribute to the host innate immune system to produce inflammatory mediators, such as cytokines. Thus, the interaction of pathogens with host cell receptors, such as integrins and Toll-like Receptors, can lead to recruitment of these molecules to domains in the plasma membrane, named membrane rafts, causing activation of the receptors and their respective cell signaling pathways, culminating in cytokine expression.Thus, the main objective of this project is to study the cellular mechanisms involved in secretion of cytokines by epithelial cells infected with P. brasiliensis. For this, during infection with P. brasiliensis yeasts, we will study the: (i) expression of integrins (alpha 3 and alpha 5) and TLRs (TLR2 and TLR4), (ii) interaction between receptors, (iii) recruitment of receptors to membrane rafts of epithelial cells, (iv) importance of each receptor in secretion of IL-6 and IL-8, and (v) activation and modulation of TLR signaling pathways and SFKs in IL-6 and IL-8 secretion.

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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)
ALCANTARA, CRISTIANE; ALMEIDA, BRUNA ROCHA; SILVA CAMPITELLI BARROS, BIANCA CARLA; ORIKAZA, CRISTINA MARY; TOLEDO, MARCOS SERGIO; SUZUKI, ERIKA. Histoplasma capsulatum chemotypes I and II induce IL-8 secretion in lung epithelial cells in distinct manners. Medical Mycology, v. 58, n. 8, p. 1169-1177, . (15/25652-6, 16/06285-5)
SILVA CAMPITELLI DE BARROS, BIANCA CARLA; ALMEIDA, BRUNA ROCHA; SUZUKI, ERIKA. Paracoccidioides brasiliensis downmodulates alpha 3 integrin levels in human lung epithelial cells in a TLR2-dependent manner. SCIENTIFIC REPORTS, v. 10, n. 1, . (19/26693-9, 16/06285-5, 15/25652-6)
ALMEIDA, BRUNA ROCHA; CAMPITELLI BARROS, BIANCA CARLA SILVA; LIGUORI ARAUJO, ANA CLARA; ALCANTARA, CRISTIANE; SUZUKI, ERIKA. Paracoccidioides species present distinct fungal adherence to epithelial lung cells and promote different IL-8 secretion levels. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 209, n. 1, . (15/25652-6, 16/06285-5)

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