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)

1 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
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]

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.

Domains: Immunology; Virology

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, 2016, 12 (8), pp.11-7. ⟨10.1371/journal.ppat.1005774⟩. ⟨pasteur-01380604⟩