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Effect of treatment with epidrugs: impact on the training of cells in the innate immune system of HIV+ patients

Grant number: 20/02354-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2020
Effective date (End): January 31, 2025
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Fabiani Gai Frantz
Grantee:Fabrícia Heloisa Cavicchioli Sugiyama
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:18/15066-0 - Epigenetic programming during chronic infectious diseases: tiring out and training the innate immune system, AP.JP2

Abstract

Epigenetics study modifications in the pattern of gene expression, although they do not promote direct changes to the DNA nucleotide sequence. Several studies have demonstrated its role in the regulation of cellular processes, including the modulation of the activation and polarization profile of cells of the immune system, such as T cells, monocytes, dendritic cells and macrophages. The training and exhaustion of cells of the innate immune system ("memory" of innate cells) are also related to epigenetic changes. Epigenetic changes are necessary for the physiological control of cell differentiation or phenotypic changes, but it has been increasingly associated with the development of several pathological processes such as autoimmune diseases and cancers. The study of how epigenetic mechanisms modulate gene expression, the understanding of how these changes participate in pathogenic processes, as well as the potential for reversing some epigenetic changes, allow the research of how drugs with regulatory action on epigenetic changes could be used in infectious disease treatments. It is known that cells in the immune system of HIV-infected patients have a profile of exhaustion and senescence that can interfere with the training of the innate immune response. Innate training occurs when there are metabolic changes and epigenetic reprogramming in innate immune cells induced by a microbial stimulus resulting in the ability of the innate immune system to respond more quickly and efficiently to a second stimulus. Thus, the objective of the project will be to evaluate the training parameters in monocytes and NK cells, comparing cells from HIV-infected patients with cells from control individuals. We intend to understand how the treatment with epidrugs modulates the training in these patients and to evaluate which epigenetic changes are present in the cells of HIV-infected patients that may interfere in the training of these cells. (AU)