Expression profile and functional analysis of TLR10 at the maternal-fetal interface in Zika virus infection

• Grant number: 24/07258-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Daniel Pereira Sousa
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/25119-7 - Maternal-fetal interface: immunopathogenesis and vaccinal intervention in viral infections, AP.TEM

Abstract

The maternal-fetal interface is a site of ongoing immunoregulation, crucial for fetal development and protection against infections. Toll-like receptors (TLRs) play an essential role in the innate recognition of pathogens, including TLR10, which, although still poorly understood, is known to trigger both inflammatory and anti-inflammatory responses. Expressed in various cells, including trophoblasts, TLR10 can form heterodimers with TLR1/2/6 via extracellular domains or homodimers (TLR10/TLR10). TLR10 is also recognized as an immunological sensor of viral infections, although its role in this context is not well established. The project aims to investigate the expression and function of TLR10 at the maternal-fetal interface and its potential in Zika virus infection. Our hypothesis is that TLR10 in trophoblasts may be involved in the immunoregulation of the inflammatory response during pregnancy. The expression of TLR10/2/1/6 will be evaluated in cultures of placental villi and monocytic lineage, stimulated with TLR2 agonist. TLR10 blockade will be performed to assess the induction of pro or anti-inflammatory cytokines. The influence of ZIKV infection will be analyzed in cultures of placental villi regarding viral load and expression of antiviral factors. Interference in TLR10 expression in THP-1 lineage and transfection of TLR10 and TLR2 genes in BeWo trophoblastic cells will be carried out to confirm its function. Additionally, TLR10 expression will be examined in placentas from mothers infected with ZIKV who had children with or without microcephaly. This analysis is essential for understanding regulation and inflammation in pregnancy, as well as being a potential strategy for modulating congenital viral infections.