Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

Autor: Ploquin MJ; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Madec Y; Institut Pasteur, Département de infection et épidémiologie, Unité de Recherche et d'Expertise Epidémiologie des Maladies Emergentes, Paris, France., Casrouge A; Institut Pasteur, Département d'immunologie, Unité Immunobiologie des cellules dendritiques, INSERM U818, Paris, France., Huot N; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Passaes C; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Lécuroux C; 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., Essat A; INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France., Boufassa F; INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France., Jacquelin B; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Jochems SP; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Petitjean G; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Angin M; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Gärtner K; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Garcia-Tellez T; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Noël N; 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., Booiman T; Academisch Medisch Centrum, Laboratory of Viral Immune Pathogenesis, Amsterdam The Netherlands., Boeser-Nunnink BD; Academisch Medisch Centrum, Laboratory of Viral Immune Pathogenesis, Amsterdam The Netherlands., Roques P; 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., Saez-Cirion A; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France., Vaslin B; 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., Dereudre-Bosquet N; 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., Barré-Sinoussi F; Institut Pasteur, Département de Virologie, Unité Régulation des infections rétrovirales, Paris, France., Ghislain M; INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France., Rouzioux C; Centre Hospitalier Universitaire Necker-Hôpitaux de Paris, Laboratoire de Virologie, Paris, France.; EA7327 Université Paris Descartes, Paris, France., Lambotte O; 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., Albert ML; Institut Pasteur, Département d'immunologie, Unité Immunobiologie des cellules dendritiques, INSERM U818, Paris, France., Goujard C; 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., Kootstra N; Academisch Medisch Centrum, Laboratory of Viral Immune Pathogenesis, Amsterdam The Netherlands., Meyer L; INSERM CESP U1018, Université Paris Saclay, Université Paris Sud, AP-HP, Le Kremlin-Bicêtre, France., Müller-Trutwin MC; Institut Pasteur, Département de Virologie, Unité HIV, Inflammation et Persistance, Paris, France.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2016 Aug 10; Vol. 12 (8), pp. e1005774. Date of Electronic Publication: 2016 Aug 10 (Print Publication: 2016).
DOI: 10.1371/journal.ppat.1005774
Abstrakt: 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.
Databáze: MEDLINE