Chiraz Atri Poster 2025

 Dr Chiraz Atri

Institut Pasteur de Tunis, Tunisia

Implication of NR4A Transcription Factors during Leishmania-Macrophage Interactions

Poster Abstract

Leishmaniasis is a parasitic disease caused by Leishmania (L.) and transmitted to humans through the bite of sandflies from the Phlebotomus genus. Leishmania employed complex strategies to evade the host's immune response and manipulate macrophage functions. Despite extensive community efforts, only a few molecules have been identified as playing a crucial role during the infectious process. Recently, nuclear receptors, e.g., NR4A subfamily, have been identified as key players in various cellular processes and diseases.

The main goal of our ongoing work is to further investigate the interplay between different NR4A members and the macrophage immune responses during L. major infection. Specifically, we aimed to assess the effect of L. major infection on NR4A recruitment in THP-1 macrophages through a kinetic time series and explored the implication of their silencing on macrophages cytokinic response. We also studied the impact of contrasted (Hyper vs hypo) virulence of L. major field isolates on the modulation of NR4A genes expression.

Our data demonstrate that the expression of NR4A genes is rapidly induced during the initial stages of infection, peaking after 2 hours. This supports that NR4A members act as Immediate Early genes in response to infection. Furthermore, the expression of NR4A in M1 and M2 macrophages, along with the effects of their silencing on cytokine production, revealed differences in their recruitment among different macrophage subpopulations within the first 24 hours of infection. Finally, our preliminary data also highlighted the impact of different L. major strains with contrasted virulence on NR4A1 and NR4A3 expression at both early and late time points of infection. These findings suggest that NR4A genes may play a crucial role in the host immune response against Leishmania parasites. Further analysis will be conducted to better decipher the impact of L. major according to its virulence on NR4A recruitment.

Biography

Chiraz Atri is a post-doctoral researcher at Institut Pasteur de Tunis. With her hybrid scientific profile as a Biologist and Bioinformatician, Chiraz is involved in several projects dealing with infectious diseases and epidemiological surveillance. Chiraz started working on Cutaneous Leishmaniasis since 2011. The main goal of her ongoing work, is to investigate host-parasite interactions. She is implicated in analysing the impact of Leishmania infection on innate immune responses through genomics and transcriptomics features. Chiraz studied the role of microRNAs and their targets in human macrophages infected with Leishmania major parasites to identify biomarkers and molecules with anti-parasitic and/or vaccine potential.