Functional biomarkers of the immune response in human tuberculosis

• Grant number: 17/05365-8
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2017 - July 31, 2019
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Fabiani Gai Frantz
• Grantee: Fabiani Gai Frantz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Tuberculosis (TB) is a bacterial infectious disease caused by Mycobacterium tuberculosis, still considered a serious public health problem. It is estimated that one-third of the world's population is infected with M. tuberculosis, with the latent form of the disease which can be reactivated. Moreover, the lack of rapid and sensitive diagnostic, inadequate adherence to treatment and the acquisition of resistance to antibiotics by bacteria, further jeopardize this frame. With this project, new molecular targets aiming diagnosis and therapy will be explored. To explore the signaling pathways of the Notch receptor and its ligands will be a challenge of our project. This pathway is described as important in maintaining the immune response and can influence the dynamics of the immunity against bacilli. Another challenge will be understand how hypomethylation of cells from innate immunity could modulate the host response to infection. Currently, the use of drugs that act by modifying the DNA methylation pattern, the "epidrugs", have been explored as modulators of the immune response in tumors. Exploring the effect of these drugs during infections, considering their possibilities of clinical use is relevant in this scenario. Therefore, we wonder to investigate those two gaps in the literature, revealing immune response pathways that can be correlated with clinical data, and thereafter, new diagnostic and treatment biomarkers could be explored in this pathology. (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)

ZAMBUZI, FABIANA ALBANI; CARDOSO-SILVA, PRISCILLA MARIANE; CASTRO, RICARDO CARDOSO; FONTANARI, CAROLINE; EMERY, FLAVIO DA SILVA; FRANTZ, FABIANI GAI. Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation. CELLS, v. 10, n. 4, APR 2021. (18/15066-0, 17/05365-8)

ESPINDOLA, MILENA S.; SOARES, LUANA S.; GALVAO-LIMA, LEONARDO J.; ZAMBUZI, FABIANA A.; CACEMIRO, MAIRA C.; BRAUER, VERONICA S.; MARZOCCHI-MACHADO, CLENI M.; GOMES, MATHEUS DE SOUZA; AMARAL, LAURENCE R.; MARTINS-FILHO, OLINDO A.; et al. Epigenetic alterations are associated with monocyte immune dysfunctions in HIV-1 infection. SCIENTIFIC REPORTS, v. 8, APR 3 2018. (11/12512-0, 11/12199-0, 17/05365-8)

CASTRO, RICARDO C.; ZAMBUZI, FABIANA A.; FONTANARI, CAROLINE; DE MORAIS, FABIANA R.; BOLLELA, VALDES R.; KUNKEL, STEVEN L.; SCHALLER, MATTHEW A.; FRANTZ, FABIANI G.. NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation. TUBERCULOSIS, v. 124, p. 10-pg., 2020-09-01. (17/05365-8)