Research Field: Biological sciences › Biology
Researcher Profile: Recognised Researcher (R2)
Application Deadline: 01/10/2022 21:00 - Europe/Athens
Location: France › Toulouse
Type Of Contract: Permanent
Job Status: Full-time
Hours Per Week: 40
Offer Starting Date: 01/11/2022
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
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.
Imai, T. et al. Identification and molecular characterization of
fractalkine receptor CX3CR1, which mediates both leukocyte migration and
adhesion. Cell 91, 521-530 (1997).
Foussat, A. et al. Fractalkine receptor expression by T lymphocyte
subpopulations and in vivo production of fractalkine in human. Eur J
Immunol 30, 87-97 (2000).
Combadiere, B., et al. The chemokine receptor CX3CR1 controls homing and
anti-viral potencies of CD8 effector-memory T lymphocytes in HIV-infected
patients. AIDS 17, 1279-1290 (2003).
Hudson, W. H. et al. Proliferating Transitory T Cells with an Effector-
like Transcriptional Signature Emerge from PD-1(+) Stem-like CD8(+) T
Cells during Chronic Infection. Immunity 51, 1043-1058 e1044 (2019).
Gordon, C. L. et al. Induction and Maintenance of CX3CR1-Intermediate
Peripheral Memory CD8(+) T Cells by Persistent Viruses and Vaccines.
Cell Rep 23, 768-782 (2018).
Gerlach, C. et al. The Chemokine Receptor CX3CR1 Defines Three Antigen-
Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance
and Homeostasis. Immunity 45, 1270-1284 (2016).
Yamauchi, T. et al. T-cell CX3CR1 expression as a dynamic blood-based
biomarker of response to immune checkpoint inhibitors. Nature
communications 12, 1402 (2021).
Yan, Y. et al. CX3CR1 identifies PD-1 therapy-responsive CD8+ T cells that
withstand chemotherapy during cancer chemoimmunotherapy. JCI insight 3
Previous work on this topic:
Mavigner, M. et al. Altered CD4+ T cell homing to the gut impairs mucosal
immune reconstitution in treated HIV-infected individuals. J Clin
Invest122, 62-69 (2012).
Loiseau, C. et al. CCR6(-) regulatory T cells blunt the restoration of
gut Tb7 cells along the CCR6-CCL20 axis in treated HIV-1-infected
individuals. Mucosal Immunol 9, 1137-1150 (2016).
Loiseau, C. et al. Increase of CXCR3+ T cells impairs Tb7 cells
recruitment in the small intestine mucosa through IFN-gamma and IL-18
during treated HIV-1 infection. J Infect Dis (2019).
Nayrac, M. et al. Tb2 cells are efficiently recruited in the gut by CCL28
as an alternative to CCL20 but do not compensate for the loss of Tb7
cells in treated HIV-1-infected individuals. Mucosal Immunol 14, 219-228
Required Research Experiences
Biological sciences › Biology
YEARS OF RESEARCH EXPERIENCE
1 - 4
REQUIRED EDUCATION LEVEL
Biological sciences: PhD or equivalent
Mutliparametric flow cytometry (BD Symphony)
Molecular biology (qPCR, NGS, RNAseq)
Virus culture in BSL3 environment
Knowledge in immuno-virology / HIV infection
Department: U1291 - Toulouse Institute for Infectious and
Inflammatory Diseases (Infinity)
Organisation Type: Higher Education Institute
Website: https: // www. infinity.inserm.fr
Postal Code: 31024
Street: 1 place, docteur Baylac