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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

Mickaël J. Ploquin 1 Yoann Madec 2 Armanda Casrouge 3 Nicolas Huot 1 Caroline Passaes 1 Camille Lécuroux 4, 5 Asma Essat 4 Faroudy Boufassa 4 Béatrice Jacquelin 1 Simon P. Jochems 1 Gaël Petitjean 1 Mathieu Angin 1 Kathleen Gärtner 1 Thalía Garcia-Tellez 1 Nicolas Noël 6 Thijs Booiman 7 Brigitte D. Boeser-Nunnink 7 Pierre Roques 6 Asier Saez-Cirion 1 Bruno Vaslin 6 Nathalie Dereudre-Bosquet 6 Françoise Barré-Sinoussi 8 Mathilde Ghislain 4 Christine Rouzioux 9 Olivier Lambotte 6 Matthew L. Albert 3 Cécile Goujard 6 Neeltje Kootstra 7 Laurence Meyer 4 Michaela C. Müller-Trutwin 1, *
* Corresponding author
1 HIV, Inflammation et persistance
2 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
3 Immunobiologie des Cellules Dendritiques
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 CEA - Commissariat à l'énergie atomique et aux énergies alternatives
6 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
7 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
8 Régulation des Infections Rétrovirales
9 Laboratoire de Virologie [CHU Necker]
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.
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Submitted on : Thursday, October 13, 2016 - 11:31:56 AM
Last modification on : Wednesday, October 14, 2020 - 4:02:17 AM

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PASTEUR | CNAM | UVSQ | ATP-IMMUN | CEA | CESP | UNIV-PARIS-SACLAY | UNIV-HESAM

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Mickaël J. Ploquin, Yoann Madec, Armanda Casrouge, Nicolas Huot, Caroline Passaes, et al.. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset. PLoS Pathogens, Public Library of Science, 2016, 12 (8), pp.11-7. ⟨10.1371/journal.ppat.1005774⟩. ⟨pasteur-01380604⟩

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