Characterization of CD200+ macrophages during Leishmania amazonensis infection

• Grant number: 25/02649-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: June 01, 2025
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Mauro Javier Cortez Véliz
• Grantee: Sandra Viviana Vargas Otalora
• Supervisor: Nathan Peters
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Calgary, Canada
• Associated to the scholarship: 22/07830-8 - Fingerprinting of CD200R+ CD200+ macrophages during Leishmania amazonensis infection, BP.DD

Abstract

Leishmaniasis, a complex parasitic disease caused by protozoa of Leishmania, involves a complex interaction between the parasite and the host immune system. Macrophages, as effector cells of innate immunity, play a central role in acting as hosts for the parasite and modulating the immune response. Phenotypic heterogeneity of macrophages, characterized by polarization towards M1 (proinflammatory) or M2 (anti-inflammatory) profiles, is crucial in disease progression. Parasites have evolved mechanisms that evade the microbicidal responses of macrophages to survive intracellularly. Studies have shown that Leishmania amazonensis amastigotes modulate immunoregulatory molecules, such as the surface ligand CD200 and its receptor (CD200R), which control the immune system. CD200 is induced in the macrophage during infection, leading to an auto-inhibitory mechanism that blocks the iNOS/NO mechanism, favoring parasite survival and proliferation. Understanding the complex relationship between the parasite, macrophages, and the immune response is fundamental to describing new therapeutic targets against leishmaniasis. This study focuses on characterizing the heterogeneity of CD200+ macrophage populations during L. amazonensis infection where, through tools such as flow cytometry and single cell RNA sequencing, we will analyze changes in CD200 expression, markers associated with M1 and M2phenotypes, their transcriptional programs, and their relationship with the CD200/CD200R axis throughout the infectious process.