Integration of NLRP12- and miR-294-mediated signals in macrophage activation and susceptibility to Leishmania infection

• Grant number: 25/04633-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sandra Marcia Muxel
• Grantee: Clara Andrade Teixeira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/08802-3 - Integrative study of Long noncoding RNAs and microRNAs in Leishmania infection, AP.R

Abstract

In this project, we aim to investigate the activity of NLRP12 and miR-294 in macrophages during infection with L. amazonensis. We hypothesize that infection with Leishmania deregulates the expression and function of NLRP12 and miR-294, reducing IL-1¿ production in macrophages and increasing susceptibility to infection. NLRP12 is a member of the NLR family that is involved in the activation of inflammasome, NF-¿B and caspase-1 and IL-1¿ production in macrophages. The microRNA-294 family is transcribed from the antisense strand of the Nlrp12 gene in mice. MiRNAs are small non-protein-coding RNAs that regulate gene expression by pairing their seed (6-9 nt) with the complementary 3'UTR sequence of the target mRNA, promoting degradation or inhibition of mRNA translation. Using NLRP12 gene knockout tools and miR-294 activity inhibition, it is possible to identify a network of signals mediated by these molecules that alter inflammasome activation and cytokine production in macrophages, increasing susceptibility to infection. By comparing models susceptible to infection with L. amazonensis, BALB/c mice to the resistant C57BL/6 model, and NLRP12 knockout mouse model, we can characterize the impact of these molecules on infection.