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Chronic disseminated dermatophytosis due to Trichophyton rubrum: role of neutrophils in the effector mechanisms and in the modulation of the adaptive response of the human infection

Grant number: 18/16146-8
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): September 01, 2018
Effective date (End): October 31, 2020
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Maria da Gloria Sousa Stafocker
Grantee:Giovanna Azevedo Celestrino
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:16/16369-1 - Chronic disseminated dermatophytosis due to Trichophyton rubrum: role of neutrophils in the effector mechanisms and in the modulation of the adaptive response of the human infection, AP.JP


Dermatophytes are fungi that cause localized superficial infections of keratinized tissues, including skin, hair and nails.Trichophyton rubrum is the most common dermatophytic agent and is able to evade or suppress the host immune response. During fungal infections, neutrophils are the primary effector cells which after activation can kill the fungi. Our previous results showed decreased functional capacity in patients with chronic and disseminated dermatophytosis (DCD) when compared to neutrophils from a control group. In addition, biopsies of skin lesions of these patients showed lack of neutrophil infiltration. The neutrophil mechanism of fungal killing is poorly understood. First, it is not known which pathogen recognition receptors (PRR) and their downsteam signaling pathways are involved in the killing of T. rubrum. Recent studies identified C-type lectin receptors (CLRs) as important family of PRR that play a central role in immunity to fungal pathogens. CLRs induce intracellular signaling that trigger several cellular responses including induction of various patterns of cytokine and chemokine expression, which in turn drives the cellular immune response into either a protective or a non-protective one. In this study, we aim to evaluate the mechanism by which neutrophils from DCD patients kill fungi as well the participation of C-type lectin receptors in the modulation of adaptive immunity (ex vivo and in situ) leading to DCD. In addition, we will evaluate the immunogenetic profile of genes related to neutrophil migration pathways and intracellular signaling pathways related to the Th17 response. Understanding the cellular and metabolic pathways involved in the fungal-neutrophil interaction will potentially provide novel information to the selection of new drug targets and development of new drugs that could improve the therapeutic approach of patients with persistent, invasive and non-invasive fungal infections, DCD included, all of them characterized by poor responses to the currently available antifungal agents. (AU)

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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)
CELESTRINO, GIOVANNA AZEVEDO; VEASEY, JOHN VERRINDER; BENARD, GIL; TEIXEIRA SOUSA, MARIA GLORIA. Host immune responses in dermatophytes infection. MYCOSES, v. 64, n. 5, . (16/16369-1, 17/26208-8, 18/16146-8)
CELESTRINO, GIOVANNA AZEVEDO; CARVALHO REIS, ANA PAULA; CRIADO, PAULO RICARDO; BENARD, GIL; TEIXEIRA SOUSA, MARIA GLORIA. Trichophyton rubrum Elicits Phagocytic and Pro-inflammatory Responses in Human Monocytes Through Toll-Like Receptor 2. FRONTIERS IN MICROBIOLOGY, v. 10, . (17/26208-8, 16/16369-1, 18/24175-8, 18/16146-8)
REIS, ANA PAULA CARVALHO; CELESTRINO, GIOVANNA AZEVEDO; IGOA, MARIANA VILLAS BOAS; JESUS, THAIS MARTINS; FRANCA, TABATA TAKAHASHI; MOREIRA, DANIEL VALERIO SILVA; RIGATO, PAULA ORDONHEZ; SATO, PAULA KEIKO; CONDINO-NETO, ANTONIO; NORONHA, IRENE L.; et al. he Dermatophyte Trichophyton rubrum Induces Neutrophil Extracellular Traps Release by Human Neutrophil. OURNAL OF FUNG, v. 8, n. 2, . (17/26208-8, 16/16369-1, 18/24175-8, 18/16146-8)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CELESTRINO, Giovanna Azevedo. Human monocytes recognition of Trichophyton rubrum: role of toll like and C-type lectin receptors. 2020. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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