title: Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.
abstract: Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Mickaël J
authors: MJ
authors: Ploquin
authors: Institut Pasteur, Département de infection et épidémiologie, Unité de Recherche et d'Expertise Epidémiologie des Maladies Emergentes, Paris, France.
authors: Yoann
authors: 0000-0002-6201-1261
authors: Y
authors: Madec
authors: Institut Pasteur, Département d'immunologie, Unité Immunobiologie des cellules dendritiques, INSERM U818, Paris, France.
authors: Armanda
authors: A
authors: Casrouge
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Nicolas
authors: N
authors: Huot
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Caroline
authors: C
authors: Passaes
authors: INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France.|Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.
authors: Camille
authors: C
authors: Lécuroux
authors: INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France.
authors: Asma
authors: A
authors: Essat
authors: INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France.
authors: Faroudy
authors: F
authors: Boufassa
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Béatrice
authors: B
authors: Jacquelin
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Simon P
authors: SP
authors: Jochems
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Gaël
authors: G
authors: Petitjean
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Mathieu
authors: M
authors: Angin
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Kathleen
authors: K
authors: Gärtner
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Thalía
authors: T
authors: Garcia-Tellez
authors: Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.|INSERM U1184, Université Paris Saclay, Université Paris Sud, Le Kremlin-Bicêtre, France.|Service de Médecine interne, Hôpitaux universitaires Paris Sud, Le Kremlin-Bicêtre, France.
authors: Nicolas
authors: 0000-0003-4055-617X
authors: N
authors: Noël
authors: Academisch Medisch Centrum, Laboratory of Viral Immune Pathogenesis, Amsterdam The Netherlands.
authors: Thijs
authors: T
authors: Booiman
authors: Academisch Medisch Centrum, Laboratory of Viral Immune Pathogenesis, Amsterdam The Netherlands.
authors: Brigitte D
authors: BD
authors: Boeser-Nunnink
authors: Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.|INSERM U1184, Université Paris Saclay, Université Paris Sud, Le Kremlin-Bicêtre, France.
authors: Pierre
authors: P
authors: Roques
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Asier
authors: A
authors: Saez-Cirion
authors: Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.|INSERM U1184, Université Paris Saclay, Université Paris Sud, Le Kremlin-Bicêtre, France.
authors: Bruno
authors: B
authors: Vaslin
authors: Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.|INSERM U1184, Université Paris Saclay, Université Paris Sud, Le Kremlin-Bicêtre, France.
authors: Nathalie
authors: N
authors: Dereudre-Bosquet
authors: Institut Pasteur, Département de Virologie, Unité Régulation des infections rétrovirales, Paris, France.
authors: Françoise
authors: F
authors: Barré-Sinoussi
authors: INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France.
authors: Mathilde
authors: M
authors: Ghislain
authors: Centre Hospitalier Universitaire Necker-Hôpitaux de Paris, Laboratoire de Virologie, Paris, France.|EA7327 Université Paris Descartes, Paris, France.
authors: Christine
authors: C
authors: Rouzioux
authors: Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.|INSERM U1184, Université Paris Saclay, Université Paris Sud, Le Kremlin-Bicêtre, France.|Service de Médecine interne, Hôpitaux universitaires Paris Sud, Le Kremlin-Bicêtre, France.
authors: Olivier
authors: O
authors: Lambotte
authors: Institut Pasteur, Département d'immunologie, Unité Immunobiologie des cellules dendritiques, INSERM U818, Paris, France.
authors: Matthew L
authors: ML
authors: Albert
authors: Commissariat à l'Energie atomique et aux énergies alternatives, Division IMVA/IDMIT/IMETI/SIV CEA, Fontenay-aux-Roses, France.|INSERM U1184, Université Paris Saclay, Université Paris Sud, Le Kremlin-Bicêtre, France.|Service de Médecine interne, Hôpitaux universitaires Paris Sud, Le Kremlin-Bicêtre, France.
authors: Cécile
authors: C
authors: Goujard
authors: Academisch Medisch Centrum, Laboratory of Viral Immune Pathogenesis, Amsterdam The Netherlands.
authors: Neeltje
authors: N
authors: Kootstra
authors: INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France.
authors: Laurence
authors: L
authors: Meyer
authors: Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
authors: Michaela C
authors: MC
authors: Müller-Trutwin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D054357:Chemokine CXCL10 / Q000378:metabolism*; D018450:Disease Progression; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000276:immunology*; D008251:Macaca; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D019562:Viral Load / Q000276:immunology; D014766:Viremia / Q000276:immunology
chemical_list: D054357:Chemokine CXCL10