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Study of immunological and epigenetic markers of extracellular vesicles and their ability to induce early immunosenescence related to HIV infection

Grant number: 19/11422-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2021
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Fabiani Gai Frantz
Grantee:Ricardo Cardoso Castro
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

The Human Immunodeficiency Virus (HIV), the cause of Acquired Immunodeficiency Syndrome (AIDS), is considered a major public health problem worldwide. By 2017, in Brazil, it is estimated that 867 thousand people living with HIV. Although there is the treatment for HIV infection, HIV + patients even on antiretroviral therapy have a constant activation of the innate and adaptive immune system, resulting in the intermittent release of mediators of inflammation. Chronic and persistent immune activation results in the exhaustion and accelerated aging of the cells of the immune system in the infected individual. Thus, these individuals present comorbidities, such as Atherosclerosis, neurodegeneration, Cancer, and others. Our hypothesis is based on the fact that Extracellular Vesicles (EVs) containing PAMPs, cytokines and epigenetic enzymes are secreted during HIV infection, and thus directly affect uninfected cells, causing them to undergo epigenetic changes associated with the phenotype of exhaustion or training of the immune system. Therefore, our goal is to evaluate the mechanisms of senescence in peripheral blood mononuclear cells of HIV-infected patients and to understand how EVs may influence the development of the immunosenescence phenotype of non-virus infected cells. In this way, this study will contribute to the understanding of mechanisms related to immunosenescence during HIV infection and will aid in the research of new molecular targets that may be part of therapy regimens aimed at reducing systemic inflammation in HIV infected individuals. (AU)

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