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Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset
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نویسنده
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ploquin m.j. ,madec y. ,casrouge a. ,huot n. ,passaes c. ,lécuroux c. ,essat a. ,boufassa f. ,jacquelin b. ,jochems s.p. ,petitjean g. ,angin m. ,gärtner k. ,garcia-tellez t. ,noël n. ,booiman t. ,boeser-nunnink b.d. ,roques p. ,saez-cirion a. ,vaslin b. ,dereudre-bosquet n. ,barré-sinoussi f. ,ghislain m. ,rouzioux c. ,lambotte o. ,albert m.l. ,goujard c. ,kootstra n. ,meyer l. ,müller-trutwin m.c.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 8
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چکیده
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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. © 2016 ploquin et al.
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آدرس
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institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, institut pasteur,département de infection et épidémiologie,unité de recherche et d’expertise epidémiologie des maladies emergentes,paris, France, institut pasteur,département d’immunologie,unité immunobiologie des cellules dendritiques,inserm u818,paris, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, 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, inserm cesp u1018,université paris saclay,université paris sud,ap-hp,le kremlin-bicêtre, France, inserm cesp u1018,université paris saclay,université paris sud,ap-hp,le kremlin-bicêtre, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris,france,liverpool school of hygiene,liverpool, United Kingdom, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, 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, academisch medisch centrum,laboratory of viral immune pathogenesis,amsterdam, Netherlands, academisch medisch centrum,laboratory of viral immune pathogenesis,amsterdam, Netherlands, 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, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France, 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, 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, institut pasteur,département de virologie,unité régulation des infections rétrovirales,paris, France, inserm cesp u1018,université paris saclay,université paris sud,ap-hp,le kremlin-bicêtre, France, centre hospitalier universitaire necker–hôpitaux de paris,laboratoire de virologie,paris,france,ea7327 université paris descartes,paris, France, 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, institut pasteur,département d’immunologie,unité immunobiologie des cellules dendritiques,inserm u818,paris, France, 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, academisch medisch centrum,laboratory of viral immune pathogenesis,amsterdam, Netherlands, inserm cesp u1018,université paris saclay,université paris sud,ap-hp,le kremlin-bicêtre, France, institut pasteur,département de virologie,unité hiv,inflammation et persistance,paris, France
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