Activation of Toll Like Receptor from Troblásticas cells in modulation of crosstalk between uterine cells: Natural Killer and Dendritic from mothers infected by HIV-1

• Grant number: 12/11956-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2013
• End date: November 30, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Estela Maris Andrade Forell Bevilacqua
• Grantee: Elaine Cristina Cardoso
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

HIV has been one of the viral pandemics that most affects women of childbearing age and consequently pregnant women. According to estimates by UNAIDS (Joint United Nations Programme on HIV / AIDS), women account for 50% of the worldwide people infected with HIV. Even in the absence of antiretroviral drugs during prenatal and other preventive measures, infection occurs in only about 20-35% of children, i.e., 65-80% of neonates do not acquire infection. These findings highlight the need for studies on virus-host relationships during pregnancy and in particular on the role of trophoblast in this context. Recent evidences indicate that trophoblast cells express Toll-like receptors (TLR) which may be a relevant tool to regulate the differentiation and activation of immune cells. In this study, we hypothesized that during viral infection by HIV, trophoblast cells are able of orchestrating an immunoregulatory environment, regulating differentiation and activation of immune cells via Toll-like receptors (TLR), and therefore, contributing to successful pregnancy and fetal protection mechanisms. More specifically, we are focusing our efforts on the hypothesis that signals from the trophoblast after activation of TLR3, TLR7, TLR8 and TLR9 during viral infection by HIV, can modulate the dialogue between uterine dendritic and Natural killer cells and production of proinflammatory cytokines. For the experimental design we are also considering the potential effect of the TLR agonists also expressed by immune cells, which might change the panorama of the inflammatory cytokines at the placental microenvironment. Our studies propose a new approach to analyze the viral infection during pregnancy evaluating trophoblast cells in the modulation of innate response and/or interference in the immune response triggered by HIV infection. We believe these data are important and may be of help to understand immune defense mechanisms of the maternal-fetal interface.