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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.

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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Ploquin MJ, Madec Y, Casrouge A, Huot N, Passaes C, Lécuroux C, Essat A, Boufassa F, Jacquelin B, Jochems SP, Petitjean G, Angin M, Gärtner K, Garcia-Tellez T, Noël N, Booiman T, Boeser-Nunnink BD, Roques P, Saez-Cirion A, Vaslin B, Dereudre-Bosquet N, Barré-Sinoussi F, Ghislain M, Rouzioux C, Lambotte O, Albert ML, Goujard C, Kootstra N, Meyer L, Müller-Trutwin MC,


Ploquin MJ, Madec Y, Casrouge A, Huot N, Passaes C, Lécuroux C, Essat A, Boufassa F, Jacquelin B, Jochems SP, Petitjean G, Angin M, Gärtner K, Garcia-Tellez T, Noël N, Booiman T, Boeser-Nunnink BD, Roques P, Saez-Cirion A, Vaslin B, Dereudre-Bosquet N, Barré-Sinoussi F, Ghislain M, Rouzioux C, Lambotte O, Albert ML, Goujard C, Kootstra N, Meyer L, Müller-Trutwin MC, (click to view)

Ploquin MJ, Madec Y, Casrouge A, Huot N, Passaes C, Lécuroux C, Essat A, Boufassa F, Jacquelin B, Jochems SP, Petitjean G, Angin M, Gärtner K, Garcia-Tellez T, Noël N, Booiman T, Boeser-Nunnink BD, Roques P, Saez-Cirion A, Vaslin B, Dereudre-Bosquet N, Barré-Sinoussi F, Ghislain M, Rouzioux C, Lambotte O, Albert ML, Goujard C, Kootstra N, Meyer L, Müller-Trutwin MC,

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PLoS pathogens 2016 08 1012(8) e1005774 doi 10.1371/journal.ppat.1005774

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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