Fingerprinting of CD200R+ CD200+ macrophages during Leishmania amazonensis infection

• Grant number: 22/07830-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): June 01, 2023
• Effective date (End): May 31, 2026
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Mauro Javier Cortez Véliz
• Grantee: Sandra Viviana Vargas Otalora
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Macrophages are the main target cells of parasites of the genus Leishmania, the causative agent of leishmaniasis. These parasites evade the microbicidal responses of macrophages to survive intracellularly. Several studies show that L. amazonensis amastigotes modulate immune-regulatory molecules, such as the surface ligand CD200 and its receptor (CD200R), a host inhibitory complex that participates in controlling the immune system. CD200 is induced in the macrophage during L. amazonensis infection, resulting in an autoinhibitory mechanism that blocks the host iNOS/NO response, favoring parasite survival and proliferation. On the other hand, macrophages have been characterized mainly in two populations (known as M1 or M2 profile), which present a broad spectrum of different subpopulations according to their localization and function. Since macrophages play a significant role in Leishmania infection, our main objective is to evaluate CD200/CD200R levels and characterize the different macrophage types phenotypically during L. amazonensis infection. Our preliminary results show that CD200 is induced and recruited at the membrane of infected macrophages for 1 hour with L. amazonensis amastigotes. Furthermore, amastigotes infection modified macrophage profiles, decreasing surface markers such as CD80+ (a marker for proinflammatory M1 profile), besides surface CD200+ recruitment. These results are part of the approach for the characterization of infected macrophages in the early stages of the amastigote-host cell interaction, where CD200 is modulated, serving as a specific marker of infection by L. amazonensis amastigotes. (AU)