Phenotype, functional properties, and gut recruitment of CX3CR1+ effector lymphocytes in HIV-1-infected individuals on antiretroviral therapy
Research unit: Toulouse Institute for Infectious and Inflammatory Diseases – Infinity INSERM UMR1291- CNRS UMR5051 – Toulouse III University
Team Viral Infections : persistence, host response, and pathophysiology
Specialty : Immunology
Scientific project manager: Prof. Pierre DELOBEL, MD, PhD
HIV-1, lymphocytes, CX3CR1, CX3CL1, gut
The gut is a key organ for HIV replication and persistence on antiretroviral therapy. Despite effective treatment, the gut immune barrier remains incompletely restored in HIV-1-infected individuals. This leaky barrier is responsible for chronic microbial translocation from the gut lumen into the bloodstream, and subsequent chronic inflammation. A vicious circle between chronic mucosal inflammation and defective immune reconstitution could be induced by antigenic stimuli from cells harboring HIV proviruses and/or from microbial products, and persistent dysregulation of immune cells recruitment to the gut mucosa. In treated HIV-1-infected individuals, the Tb7/Treg ratio remains imbalanced, while Tb and effector memory CD8+ T cells are efficiently recruited in the gut mucosa.
The CX3CL1-CX3CR1 chemotactic axis is involved in the recruitment of terminally differentiated effector lymphocytes among CD8+T cells, gd T cells, and NK cells that share CX3CR1 expression. CX3CR1 ligand, the CX3CL1 chemokine, is produced by epithelial and endothelial in the gut mucosa. CX3CR1+ effector lymphocytes could have retained cytotoxic properties without being fully exhausted and could thus play a key role in antiviral response in tissues.
We plan to perform in depth characterization of CX3CR1+ effector lymphocytes, as well as CX3CL1 expression, from blood and gut samples already collected in the ANRS EP61 GALT study. This study had recruited 42 HIV-1-infected individuals on antiretroviral therapy, and 42 uninfected controls, for whom duodenal, ileal, and colonic biopsies have been collected, in parallel to blood samples. CX3CR1+ CD8+ T cells, gd T cells, and NK cells will be characterized in blood and gut samples regarding their phenotype and function. CX3CL1 production in the gut mucosa will also be studied, notably the mechanisms regulating CX3CL1 expression using ex-vivo models of gut histocultures and primary enterocytes cultures.
This study will allow in depth characterization of the phenotype and functional properties of effector CX3CR1+ CD8+ T cells, gd T cells, and NK cells, and information on the effectiveness of the CX3CL1-CX3CR1 axis for immune cells recruitment to the gut in the setting of HIV-1 infection.
Previous work on this topic:
Biological sciences › Biology
1 - 4Offer Requirements
Biological sciences: PhD or equivalent
Mutliparametric flow cytometry (BD Symphony)
Molecular biology (qPCR, NGS, RNAseq)
Virus culture in BSL3 environmentSpecific Requirements
Knowledge in immuno-virology / HIV infectionContact Information