Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• PLoS pathogens, 2016-08, Vol.12 (8), p.e1005774-e1005774

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.