Project

Go Back to Project List
#20011 : Dissecting phenotypic heterogeneity and immune responses of macrophages during Leishmania Infection via Single-Cell RNA Sequencing
Topics: Single Cells
Origin: IP
Project type: Expertise

Name of Applicant: Eric Prina
Date of application: 21-07-2025
Unit: Molecular Parasitology and Signaling
Location: 62-02-05c
Phone: 01 7653 5863
@ Mail: eric.prina@pasteur.fr
@ PI-Mail: gerald.spaeth@pasteur.fr

Project context and summary:

Leishmania is an intracellular protozoan parasite that establishes infection within host macrophages by subverting their immune defenses and reprogramming cellular metabolism. Previous studies at the bulk population level, including transcriptomic analyses, have revealed significant alterations in macrophage gene expression upon infection. These include suppression of pro-inflammatory pathways and modulation of macrophage polarization states, facilitating parasite survival and replication.
However, macrophages are inherently heterogeneous, and bulk approaches — even when applied to relatively homogenous bone marrow-derived macrophages — mask cell-to-cell variability that may be critical for understanding host-pathogen dynamics. To address this, we aim to perform single-cell RNA sequencing (scRNA-seq) using the 10x Genomics platform on uninfected and Leishmania-infected macrophages. This approach will enable high-resolution dissection of macrophage heterogeneity, with a focus on characterizing distinct transcriptional profiles and polarization states (e.g., M1-like vs. M2-like phenotypes) in response to the intracellular amastigote stage of Leishmania.
By profiling thousands of individual cells per condition, we seek to uncover specific macrophage subpopulations, transcriptional trajectories, and infection-induced states that contribute to Leishmania persistence or clearance, offering new insights into host-pathogen interactions and immune evasion strategies at the single-cell level.


Related team publications:
Rajan, K.S., et al., Structural and mechanistic insights into the function of Leishmania ribosome lacking a single pseudouridine modification. Cell Rep, [2024]. 43(5): p. 114203.DOI:10.1016/j.celrep.2024.114203 2.
Lecoeur, H., et al., Going ballistic: Leishmania nuclear subversion of host cell plasticity. Trends Parasitol, [2022]. 38(3): p. 205-216.DOI:10.1016/j.pt.2021.09.009
Lecoeur, H., et al., Leishmania amazonensis Subverts the Transcription Factor Landscape in Dendritic Cells to Avoid Inflammasome Activation and Stall Maturation. Frontiers in Immunology, [2020]. 11.DOI:10.3389/fimmu.2020.01098
Service Delivery
Manager: marc.monot@pasteur.fr
Status: Quotation sent


Go Back to Project List