Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals

Autor: Fatima-Ezzahra L’Faqihi, Pierre Delobel, Jacques Izopet, Christophe Pasquier, Mary Requena, Jacques Amar, Martine Dubois, Patrice Massip, Maud Mavigner, Bruno Marchou, Pascale Klopp, Karl Barange, Laurent Alric, Michelle Cazabat, Jean-Pierre Vinel
Přispěvatelé: Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], GeT-Sante, Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR50, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pagès, Nathalie
Rok vydání: 2011
Předmět:
MESH: CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes
Integrin beta Chains
[SDV]Life Sciences [q-bio]
MESH: Cell Movement / immunology
HIV Infections
Systemic inflammation
MESH: Antiretroviral Therapy
Highly Active
MESH: Integrin beta Chains / metabolism
MESH: Th17 Cells / immunology
MESH: HIV-1
Intestinal mucosa
Cell Movement
T-Lymphocyte Subsets
Antiretroviral Therapy
Highly Active
Intestine
Small
Intestinal Mucosa
education.field_of_study
MESH: Immunity
Mucosal / drug effects
MESH: RNA
Messenger / metabolism
MESH: Intestine
Small / immunology
General Medicine
MESH: Case-Control Studies
MESH: T-Lymphocyte Subsets / pathology
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Chemokines
CC
MESH: T-Lymphocyte Subsets / immunology
MESH: RNA
Messenger / genetics
medicine.symptom
MESH: Receptors
CCR / metabolism
Research Article
MESH: Chemokines
CC / metabolism
T cell
Population
MESH: HIV Infections / drug therapy
MESH: Chemokines
CC / genetics
Biology
MESH: HIV Infections / pathology
Receptors
CCR
Immune system
MESH: HIV Infections / genetics
medicine
Humans
MESH: Intestinal Mucosa / immunology
RNA
Messenger
education
Immunity
Mucosal
MESH: Humans
MESH: Th17 Cells / pathology
MESH: Intestine
Small / pathology
MESH: CD4-Positive T-Lymphocytes / pathology
Gut-specific homing
Small intestine
Case-Control Studies
Immunology
HIV-1
Th17 Cells
Homing (hematopoietic)
MESH: Intestinal Mucosa / pathology
MESH: HIV Infections / immunology
Zdroj: Journal of Clinical Investigation
Journal of Clinical Investigation, American Society for Clinical Investigation, 2012, 122 (1), pp.62-69. ⟨10.1172/JCI59011⟩
Journal of Clinical Investigation, 2012, 122 (1), pp.62-69. ⟨10.1172/JCI59011⟩
ISSN: 1558-8238
0021-9738
DOI: 10.1172/JCI59011⟩
Popis: International audience; Depletion of CD4+ T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD4+ T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD4+ T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD4+ T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR9+β7+ CD4+ T cells - a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense - correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD4+ T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART.
Databáze: OpenAIRE
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