PLoS Pathogens (Aug 2016)

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,
  • Yoann Madec,
  • Armanda Casrouge,
  • Nicolas Huot,
  • Caroline Passaes,
  • Camille Lécuroux,
  • Asma Essat,
  • Faroudy Boufassa,
  • Béatrice Jacquelin,
  • Simon P Jochems,
  • Gaël Petitjean,
  • Mathieu Angin,
  • Kathleen Gärtner,
  • Thalía Garcia-Tellez,
  • Nicolas Noël,
  • Thijs Booiman,
  • Brigitte D Boeser-Nunnink,
  • Pierre Roques,
  • Asier Saez-Cirion,
  • Bruno Vaslin,
  • Nathalie Dereudre-Bosquet,
  • Françoise Barré-Sinoussi,
  • Mathilde Ghislain,
  • Christine Rouzioux,
  • Olivier Lambotte,
  • Matthew L Albert,
  • Cécile Goujard,
  • Neeltje Kootstra,
  • Laurence Meyer,
  • Michaela C Müller-Trutwin

DOI
https://doi.org/10.1371/journal.ppat.1005774
Journal volume & issue
Vol. 12, no. 8
p. e1005774

Abstract

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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.