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, 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

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. CXCL10/IP-10 dynamics in blood before…
Fig 1. CXCL10/IP-10 dynamics in blood before HIV-1 infection and during the early infection, and its impact on the CD4 T-cells count.
IP-10 levels were determined in sera from HIV+ individuals enrolled in the Amsterdam Cohort Studies on HIV/AIDS. A. Plasma IP-10 levels. The numbers of patients per group are indicated. B. Longitudinal follow-up of the same 16 individuals. C. Positive correlation between IP-10 concentrations and viremia at PHI. D. Positive correlation between IP-10 concentrations and viremia at M3 post SC. E. Impact of pre-infection blood IP-10 concentrations on the CD4 T-cells count after seroconversion. F. Impact of M3 blood IP-10 concentrations on the CD4 T-cells count after seroconversion. E and F: Kaplan Meier survival analysis. Pre-inf. = Pre-infection (median 11 months before seroconversion), PHI = Primary HIV-1 infection, M3 and M6 = 3 and 6 months post seroconversion. * p<0.05, ** p<0.001, **** p<0.00001
Fig 2. Relationship between blood IP-10 levels…
Fig 2. Relationship between blood IP-10 levels and sCD163 during the early stages of HIV-1 infection.
Here are displayed the correlations between IP-10 concentrations and sCD163 concentrations before infection (A), during PHI (B), at M3 (C) and at M6 (D). PHI = primary HIV infection (M0), M3 = 3 months post alleged date of seronconversion, M6 = 6 months post alleged date of seronconversion in the Amsterdam Cohort (ACS). Pearson R coefficient of correlation and p values are shown on each plot.
Fig 3. Relationship between plasma IP-10 levels…
Fig 3. Relationship between plasma IP-10 levels and cell-associated DNA levels during primary HIV-1 infection.
A. IP-10 plasma concentrations stratified on cell-associated DNA levels during PHI (M0). B. Correlation between IP-10 concentrations and cell-associated DNA levels during PHI (M0). M0 = primary HIV-1 infection and time of inclusion (Fiebig stage III/IV).
Fig 4. Blood IP-10 levels in patients…
Fig 4. Blood IP-10 levels in patients with controlled HIV viremia.
A. IP-10 levels were determined in plasma in a longitudinal study, before treatment initiation and after >24 months of antiretroviral treatment, in comparison to HIV-negative individuals. The median (IQR) IP-10 values were 35.3 (10.9–51.6), 190.2 (78.3–269.7) and 97 (63.4–141.7) in HIV-, cART-naïve (VIR) and cART-treated individuals, respectively. IP-10 levels fell in cART-treated patients. B. Comparison of IP-10 levels during primary (PHI), post-acute (M6) and chronic HIV-1 infection (HIC, VIR) by comparison with cART-treated patients. HIC<50 and HIC>50 respectively represent HIV controllers with HIV RNA < and > 50 copy numbers/ml. C. Correlation between plasma IP-10 levels and CD4 cell counts during treatment. D. Correlation between plasma IP-10 levels and CD4 counts during treatment, considering only individuals with CD4>500 (25 patients). BL = baseline levels before antiretroviral treatment, cART = combination antiretroviral treatment, HIV- = HIV negative, PHI M0 = Primary HIV-1 infection time of enrollment in the PRIMO cohort, M6 = 6 months post M0/PHI, VIR = viremic cART-naïve patients, HIC = HIV controllers, ***p<0.0001, ****p<0.00001. n = number of individuals.
Fig 5. Dynamics of IP-10 levels in…
Fig 5. Dynamics of IP-10 levels in viremic and aviremic animals.
IP-10 levels in plasma were determined in a longitudinal study, before infection and after SIVmac251 challenge in cynomolgus macaques. Values are expressed as the fold change from baseline (median of 3 to 4 values obtained before infection). A. IP-10 dynamics in 27 viremic and 5 SIV-exposed aviremic animals are shown (median and interquartile range). The latter had no detectable SIVmac DNA in lymph nodes. B. Blood IP-10 dynamics in 2 aviremic animals with detectable cell-associated DNA in lymphoid tissues. Animals AX414 and 30845 were inoculated intrarectally with 5 and 50 AID50 of SIVmac251, respectively. PCR+ = detectable lymph node cell-associated SIVmac DNA on day 14 p.i., PCR neg = undetectable lymph node cell-associated SIVmac DNA.
Fig 6. Dynamics of CXCR3+ T-cells and…
Fig 6. Dynamics of CXCR3+ T-cells and blood IP-10 levels during pathogenic and non-pathogenic SIV infections.
A. CXCR3 expression levels as mean intensity of fluorescence (MIF) in rhesus macaques (n = 8) and AGM (n = 18) peripheral blood cell subsets before SIV inoculation. B. Blood IP-10 dynamics in 5 rhesus macaques versus AGMs (n = 18, median is shown here) IP-10 levels in plasma were determined in a longitudinal study, before infection and after SIVmac251 or SIVagm.sab92018 challenge in macaques or in AGMs, respectively. IP-10 values are expressed as the fold change from baseline (median of 3 to 4 values obtained before infection). (C-F). CXCR3 expression dynamics from SIVmac infected cynomolgus macaques (n = 3–6) and from SIVagm-infected AGMs (n = 3–6) C. Dynamics of CXCR3 expression in LN naïve CD4+ T cells upon SIV infection. D. Dynamics of CXCR3 expression in LN memory CD4+ T cells upon SIV infection. (E-F). Flow cytometry analysis of internalization levels of CXCR3 in lymph node CD4 T cells in cynomolgus macaques (n = 4) and in African green monkeys (n = 3). Plots of scatter measurements and CXCR3 staining are shown here. Each plot represents an animal.
Fig 7. Cellular gene expression profiles in…
Fig 7. Cellular gene expression profiles in the intestine.
A-L. Cellular gene expression levels were evaluated in CD4neg and CD4pos leukocytes from 4 distinct segments of the intestine of SIV+ non-human primates, i.e. rhesus macaques (n = 5) and African green monkeys (n = 5) on day 65 p.i. Raw values are represented. A. IP-10 gene expression. B.CXCR3 gene expression. C. Correlation between blood IP-10 levels and IP-10 gene expression in the upper intestine. IP-10 gene expression levels were normalized to expression in the rectum of each animal. IP-10 levels in blood are expressed as the fold change from baseline. (D-F) CD14, CD68 and CD163 gene expression levels were evaluated in CD4neg and CD4+ leukocytes from different segments of the digestive tract of SIV+ non-human primates obtained at necropsy (day 65 p.i.). G. Correlation between CD14 and IP-10 gene expression levels in the small intestine. H. Correlation between CD68 and IP-10 gene expression levels in the small intestine. I. Correlation between CD163 and IP-10 gene expression levels in the small intestine. J.RORc gene expression levels in CD4+ leukocytes from the small intestine. K. Correlation between RORc and IP-10 gene expression levels. L. Correlation between blood IP-10 levels and RORc gene expression levels in the small intestine. MAC = SIV-infected rhesus macaques (black), AGM = SIV-infected African Green Monkeys (blue).
Fig 8. IP-10 positive cells in jejunum…
Fig 8. IP-10 positive cells in jejunum of chronically SIVmac-infected macaques.
(a) confocal image of a jejunum section stained for CD68 (green), IP-10 (red) and total nucleus (blue). The picture represents the distribution of IP-10+ cells in jejunum of chronically infected macaques (240 dpi) (representative picture for one animal out of 3 animals studied). IP-10+ cells were found in the lamina propria around and in the villi as well as at the top of the villi. Most IP-10+ cells were CD68 negative. A fraction of CD68+ cells produced IP-10. Cells were often organized in clusters. (B) Magnification showing IP-10+ cells negative for CD68 found at the bottom of the villus. The morphology evoke T cells. (C) Magnification showing IP-10+ positive for CD68+. (D) Magnification showing IP-10+ cells organized in a cluster. Many IP-10+ cells in these clusters were CD68+. Pictures were obtained using a leica SP8 confocal microscope. All pictures were analyzed with ImageJ software.

References

    1. Ploquin M.J., Silvestri G., and Muller-Trutwin M., Immune activation in HIV infection: what can the natural hosts of simian immunodeficiency virus teach us? Curr Opin HIV AIDS, 2016. 11(2): p. 201–8. 10.1097/COH.0000000000000238
    1. Kuller L.H., Tracy R., Belloso W., De Wit S., Drummond F., Lane H.C., Ledergerber B., Lundgren J., Neuhaus J., Nixon D., Paton N.I., and Neaton J.D., Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS medicine, 2008. 5(10): p. e203 10.1371/journal.pmed.0050203
    1. Rajasuriar R., Wright E., and Lewin S.R., Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage. Curr Opin HIV AIDS, 2015. 10(1): p. 35–42. 10.1097/COH.0000000000000118
    1. Sandler N.G. and Douek D.C., Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol, 2012. 10(9): p. 655–66. 10.1038/nrmicro2848
    1. Brenchley J.M., Paiardini M., Knox K.S., Asher A.I., Cervasi B., Asher T.E., Scheinberg P., Price D.A., Hage C.A., Kholi L.M., Khoruts A., Frank I., Else J., Schacker T., Silvestri G., and Douek D.C., Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood, 2008. 112(7): p. 2826–35. 10.1182/blood-2008-05-159301
    1. Estes J.D., Harris L.D., Klatt N.R., Tabb B., Pittaluga S., Paiardini M., Barclay G.R., Smedley J., Pung R., Oliveira K.M., Hirsch V.M., Silvestri G., Douek D.C., Miller C.J., Haase A.T., Lifson J., and Brenchley J.M., Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS pathogens, 2010. 6(8): p. e1001052 10.1371/journal.ppat.1001052
    1. Pandrea I.V., Gautam R., Ribeiro R.M., Brenchley J.M., Butler I.F., Pattison M., Rasmussen T., Marx P.A., Silvestri G., Lackner A.A., Perelson A.S., Douek D.C., Veazey R.S., and Apetrei C., Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol, 2007. 179(5): p. 3035–46.
    1. Paiardini M., Frank I., Pandrea I., Apetrei C., and Silvestri G., Mucosal immune dysfunction in AIDS pathogenesis. AIDS Rev, 2008. 10(1): p. 36–46.
    1. Bosinger S.E., Li Q., Gordon S.N., Klatt N.R., Duan L., Xu L., Francella N., Sidahmed A., Smith A.J., Cramer E.M., Zeng M., Masopust D., Carlis J.V., Ran L., Vanderford T.H., Paiardini M., Isett R.B., Baldwin D.A., Else J.G., Staprans S.I., Silvestri G., Haase A.T., and Kelvin D.J., Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. The Journal of clinical investigation, 2009. 119(12): p. 3556–72. 10.1172/JCI40115
    1. Campillo-Gimenez L., Laforge M., Fay M., Brussel A., Cumont M.C., Monceaux V., Diop O., Levy Y., Hurtrel B., Zaunders J., Corbeil J., Elbim C., and Estaquier J., Nonpathogenesis of simian immunodeficiency virus infection is associated with reduced inflammation and recruitment of plasmacytoid dendritic cells to lymph nodes, not to lack of an interferon type I response, during the acute phase. Journal of virology, 2010. 84(4): p. 1838–46. 10.1128/JVI.01496-09
    1. Diop O.M., Ploquin M.J., Mortara L., Faye A., Jacquelin B., Kunkel D., Lebon P., Butor C., Hosmalin A., Barre-Sinoussi F., and Muller-Trutwin M.C., Plasmacytoid dendritic cell dynamics and alpha interferon production during Simian immunodeficiency virus infection with a nonpathogenic outcome. J Virol, 2008. 82(11): p. 5145–52. 10.1128/JVI.02433-07
    1. Harris L.D., Tabb B., Sodora D.L., Paiardini M., Klatt N.R., Douek D.C., Silvestri G., Muller-Trutwin M., Vasile-Pandrea I., Apetrei C., Hirsch V., Lifson J., Brenchley J.M., and Estes J.D., Downregulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques. Journal of virology, 2010. 84(15): p. 7886–91. 10.1128/JVI.02612-09
    1. Jacquelin B., Mayau V., Targat B., Liovat A.S., Kunkel D., Petitjean G., Dillies M.A., Roques P., Butor C., Silvestri G., Giavedoni L.D., Lebon P., Barre-Sinoussi F., Benecke A., and Muller-Trutwin M.C., Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. The Journal of clinical investigation, 2009. 119(12): p. 3544–55. 10.1172/JCI40093
    1. Jacquelin B., Petitjean G., Kunkel D., Liovat A.S., Jochems S.P., Rogers K.A., Ploquin M.J., Madec Y., Barre-Sinoussi F., Dereuddre-Bosquet N., Lebon P., Le Grand R., Villinger F., and Muller-Trutwin M., Innate immune responses and rapid control of inflammation in African green monkeys treated or not with interferon-alpha during primary SIVagm infection. PLoS Pathog, 2014. 10(7): p. e1004241 10.1371/journal.ppat.1004241
    1. Kornfeld C., Ploquin M.J., Pandrea I., Faye A., Onanga R., Apetrei C., Poaty-Mavoungou V., Rouquet P., Estaquier J., Mortara L., Desoutter J.F., Butor C., Le Grand R., Roques P., Simon F., Barre-Sinoussi F., Diop O.M., and Muller-Trutwin M.C., Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest, 2005. 115(4): p. 1082–91.
    1. Diop O.M., Gueye A., Dias-Tavares M., Kornfeld C., Faye A., Ave P., Huerre M., Corbet S., Barre-Sinoussi F., and Muller-Trutwin M.C., High levels of viral replication during primary simian immunodeficiency virus SIVagm infection are rapidly and strongly controlled in African green monkeys. J Virol, 2000. 74(16): p. 7538–47.
    1. Liovat A.S., Rey-Cuille M.A., Lecuroux C., Jacquelin B., Girault I., Petitjean G., Zitoun Y., Venet A., Barre-Sinoussi F., Lebon P., Meyer L., Sinet M., and Muller-Trutwin M., Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection. PLoS ONE, 2012. 7(10): p. e46143 10.1371/journal.pone.0046143
    1. Durudas A., Chen H.L., Gasper M.A., Sundaravaradan V., Milush J.M., Silvestri G., Johnson W., Giavedoni L.D., and Sodora D.L., Differential innate immune responses to low or high dose oral SIV challenge in Rhesus macaques. Current HIV research, 2011. 9(5): p. 276–88.
    1. Simmons R.P., Scully E.P., Groden E.E., Arnold K.B., Chang J.J., Lane K., Lifson J., Rosenberg E., Lauffenburger D.A., and Altfeld M., HIV-1 infection induces strong production of IP-10 through TLR7/9-dependent pathways. Aids, 2013. 27(16): p. 2505–17. 10.1097/01.aids.0000432455.06476.bc
    1. Allers K., Fehr M., Conrad K., Epple H.J., Schurmann D., Geelhaar-Karsch A., Schinnerling K., Moos V., and Schneider T., Macrophages accumulate in the gut mucosa of untreated HIV-infected patients. J Infect Dis, 2014. 209(5): p. 739–48. 10.1093/infdis/jit547
    1. Zalar A., Figueroa M.I., Ruibal-Ares B., Bare P., Cahn P., de Bracco M.M., and Belmonte L., Macrophage HIV-1 infection in duodenal tissue of patients on long term HAART. Antiviral Res, 2010. 87(2): p. 269–71. 10.1016/j.antiviral.2010.05.005
    1. Gosselin A., Monteiro P., Chomont N., Diaz-Griffero F., Said E.A., Fonseca S., Wacleche V., El-Far M., Boulassel M.R., Routy J.P., Sekaly R.P., and Ancuta P., Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. Journal of immunology, 2010. 184(3): p. 1604–16.
    1. Khoury G., Anderson J.L., Fromentin R., Hartogensis W., Smith M.Z., Bacchetti P., Hecht F.M., Chomont N., Cameron P.U., Deeks S.G., and Lewin S.R., Persistence of integrated HIV DNA in CXCR3 + CCR6 + memory CD4+ T-cells in HIV-infected individuals on antiretroviral therapy. Aids, 2016.
    1. Foley J.F., Yu C.-R., Solow R., Yacobucci M., Peden K.W.C., and Farber J.M., Roles for CXC Chemokine Ligands 10 and 11 in Recruiting CD4+ T Cells to HIV-1-Infected Monocyte-Derived Macrophages, Dendritic Cells, and Lymph Nodes. J Immunol, 2005. 174(8): p. 4892–4900.
    1. Burdo T.H., Lentz M.R., Autissier P., Krishnan A., Halpern E., Letendre S., Rosenberg E.S., Ellis R.J., and Williams K.C., Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis, 2011. 204(1): p. 154–63. 10.1093/infdis/jir214
    1. Sandler N.G. and Sereti I., Can early therapy reduce inflammation? Curr Opin HIV AIDS, 2014. 9(1): p. 72–9. 10.1097/COH.0000000000000020
    1. Lundgren J.D., Babiker A.G., Gordin F., Emery S., Grund B., Sharma S., Avihingsanon A., Cooper D.A., Fatkenheuer G., Llibre J.M., Molina J.M., Munderi P., Schechter M., Wood R., Klingman K.L., Collins S., Lane H.C., Phillips A.N., and Neaton J.D., Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med, 2015. 373(9): p. 795–807. 10.1056/NEJMoa1506816
    1. Bruel T., Hamimi C., Dereuddre-Bosquet N., Cosma A., Shin S.Y., Corneau A., Versmisse P., Karlsson I., Malleret B., Targat B., Barre-Sinoussi F., Le Grand R., Pancino G., Saez-Cirion A., and Vaslin B., Long-term control of simian immunodeficiency virus (SIV) in cynomolgus macaques not associated with efficient SIV-specific CD8+ T-cell responses. J Virol, 2015. 89(7): p. 3542–56. 10.1128/JVI.03723-14
    1. Bourry O., Mannioui A., Sellier P., Roucairol C., Durand-Gasselin L., Dereuddre-Bosquet N., Benech H., Roques P., and Le Grand R., Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion. Retrovirology, 2010. 7: p. 78 10.1186/1742-4690-7-78
    1. Beq S., Nugeyre M.T., Ho Tsong Fang R., Gautier D., Legrand R., Schmitt N., Estaquier J., Barre-Sinoussi F., Hurtrel B., Cheynier R., and Israel N., IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. Journal of immunology, 2006. 176(2): p. 914–22.
    1. Gueye A., Diop O.M., Ploquin M.J., Kornfeld C., Faye A., Cumont M.C., Hurtrel B., Barre-Sinoussi F., and Muller-Trutwin M.C., Viral load in tissues during the early and chronic phase of non-pathogenic SIVagm infection. J Med Primatol, 2004. 33(2): p. 83–97.
    1. Mowat A.M. and Agace W.W., Regional specialization within the intestinal immune system. Nat Rev Immunol, 2014. 14(10): p. 667–85. 10.1038/nri3738
    1. Antonelli A., Ferrari S.M., Giuggioli D., Ferrannini E., Ferri C., and Fallahi P., Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmun Rev, 2014. 13(3): p. 272–80. 10.1016/j.autrev.2013.10.010
    1. Hilkens C.M., Schlaak J.F., and Kerr I.M., Differential responses to IFN-alpha subtypes in human T cells and dendritic cells. J Immunol, 2003. 171(10): p. 5255–63.
    1. Wenzel J., Worenkamper E., Freutel S., Henze S., Haller O., Bieber T., and Tuting T., Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol, 2005. 205(4): p. 435–42.
    1. Mavigner M., Cazabat M., Dubois M., L'Faqihi F.E., Requena M., Pasquier C., Klopp P., Amar J., Alric L., Barange K., Vinel J.P., Marchou B., Massip P., Izopet J., and Delobel P., Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals. J Clin Invest, 2012. 122(1): p. 62–9. 10.1172/JCI59011
    1. Hartigan-O'Connor D.J., Hirao L.A., McCune J.M., and Dandekar S., Th17 cells and regulatory T cells in elite control over HIV and SIV. Curr Opin HIV AIDS, 2011. 6(3): p. 221–7. 10.1097/COH.0b013e32834577b3
    1. Ploquin M.J., Desoutter J.F., Santos P.R., Pandrea I., Diop O.M., Hosmalin A., Butor C., Barre-Sinoussi F., and Muller-Trutwin M.C., Distinct expression profiles of TGF-beta1 signaling mediators in pathogenic SIVmac and non-pathogenic SIVagm infections. Retrovirology, 2006. 3: p. 37
    1. Cecchinato V., Trindade C.J., Laurence A., Heraud J.M., Brenchley J.M., Ferrari M.G., Zaffiri L., Tryniszewska E., Tsai W.P., Vaccari M., Parks R.W., Venzon D., Douek D.C., O'Shea J.J., and Franchini G., Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol, 2008. 1(4): p. 279–88. 10.1038/mi.2008.14
    1. Favre D., Lederer S., Kanwar B., Ma Z.M., Proll S., Kasakow Z., Mold J., Swainson L., Barbour J.D., Baskin C.R., Palermo R., Pandrea I., Miller C.J., Katze M.G., and McCune J.M., Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog, 2009. 5(2): p. e1000295 10.1371/journal.ppat.1000295
    1. Berry M.P., Graham C.M., McNab F.W., Xu Z., Bloch S.A., Oni T., Wilkinson K.A., Banchereau R., Skinner J., Wilkinson R.J., Quinn C., Blankenship D., Dhawan R., Cush J.J., Mejias A., Ramilo O., Kon O.M., Pascual V., Banchereau J., Chaussabel D., and O'Garra A., An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 2010. 466(7309): p. 973–7. 10.1038/nature09247
    1. Hazenberg M.D., Otto S.A., van Benthem B.H., Roos M.T., Coutinho R.A., Lange J.M., Hamann D., Prins M., and Miedema F., Persistent immune activation in HIV-1 infection is associated with progression to AIDS. Aids, 2003. 17(13): p. 1881–8.
    1. Lajoie J., Juno J., Burgener A., Rahman S., Mogk K., Wachihi C., Mwanjewe J., Plummer F.A., Kimani J., Ball T.B., and Fowke K.R., A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers. Mucosal Immunol, 2012. 5(3): p. 277–87. 10.1038/mi.2012.7
    1. Lajoie J., Kimani M., Plummer F.A., Nyamiobo F., Kaul R., Kimani J., and Fowke K.R., Association of sex work with reduced activation of the mucosal immune system. J Infect Dis, 2014. 210(2): p. 319–29. 10.1093/infdis/jiu023
    1. Kahle E.M., Bolton M., Hughes J.P., Donnell D., Celum C., Lingappa J.R., Ronald A., Cohen C.R., de Bruyn G., Fong Y., Katabira E., McElrath M.J., and Baeten J.M., Plasma cytokine levels and risk of HIV type 1 (HIV-1) transmission and acquisition: a nested case-control study among HIV-1-serodiscordant couples. J Infect Dis, 2015. 211(9): p. 1451–60. 10.1093/infdis/jiu621
    1. Cheret A., Nembot G., Melard A., Lascoux C., Slama L., Miailhes P., Yeni P., Abel S., Avettand-Fenoel V., Venet A., Chaix M.L., Molina J.M., Katlama C., Goujard C., Tamalet C., Raffi F., Lafeuillade A., Reynes J., Ravaux I., Hoen B., Delfraissy J.F., Meyer L., and Rouzioux C., Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial. Lancet Infect Dis, 2015. 15(4): p. 387–96. 10.1016/S1473-3099(15)70021-6
    1. Qin S., Fallert Junecko B.A., Trichel A.M., Tarwater P.M., Murphey-Corb M.A., Kirschner D.E., and Reinhart T.A., Simian immunodeficiency virus infection alters chemokine networks in lung tissues of cynomolgus macaques: association with Pneumocystis carinii infection. Am J Pathol, 2010. 177(3): p. 1274–85. 10.2353/ajpath.2010.091288
    1. Reinhart T.A., Fallert B.A., Pfeifer M.E., Sanghavi S., Capuano S. 3rd, Rajakumar P., Murphey-Corb M., Day R., Fuller C.L., and Schaefer T.M., Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. Blood, 2002. 99(9): p. 3119–28.
    1. Lemos M.P., Lama J.R., Karuna S.T., Fong Y., Montano S.M., Ganoza C., Gottardo R., Sanchez J., and McElrath M.J., The inner foreskin of healthy males at risk of HIV infection harbors epithelial CD4+ CCR5+ cells and has features of an inflamed epidermal barrier. PLoS One, 2014. 9(9): p. e108954 10.1371/journal.pone.0108954
    1. Cameron P.U., Saleh S., Sallmann G., Solomon A., Wightman F., Evans V.A., Boucher G., Haddad E.K., Sekaly R.P., Harman A.N., Anderson J.L., Jones K.L., Mak J., Cunningham A.L., Jaworowski A., and Lewin S.R., Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton. Proc Natl Acad Sci U S A, 2010. 107(39): p. 16934–9. 10.1073/pnas.1002894107
    1. Heise C., Vogel P., Miller C.J., Halsted C.H., and Dandekar S., Simian immunodeficiency virus infection of the gastrointestinal tract of rhesus macaques. Functional, pathological, and morphological changes. Am J Pathol, 1993. 142(6): p. 1759–71.
    1. Veazey R.S., DeMaria M., Chalifoux L.V., Shvetz D.E., Pauley D.R., Knight H.L., Rosenzweig M., Johnson R.P., Desrosiers R.C., and Lackner A.A., Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science, 1998. 280(5362): p. 427–31.
    1. Yukl S.A., Gianella S., Sinclair E., Epling L., Li Q., Duan L., Choi A.L., Girling V., Ho T., Li P., Fujimoto K., Lampiris H., Hare C.B., Pandori M., Haase A.T., Gunthard H.F., Fischer M., Shergill A.K., McQuaid K., Havlir D.V., and Wong J.K., Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis, 2010. 202(10): p. 1553–61. 10.1086/656722
    1. Yukl S.A., Shergill A.K., Ho T., Killian M., Girling V., Epling L., Li P., Wong L.K., Crouch P., Deeks S.G., Havlir D.V., McQuaid K., Sinclair E., and Wong J.K., The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J Infect Dis, 2013. 208(8): p. 1212–20. 10.1093/infdis/jit308
    1. Angelovich T.A., Hearps A.C., Maisa A., Martin G.E., Lichtfuss G.F., Cheng W.J., Palmer C.S., Landay A.L., Crowe S.M., and Jaworowski A., Viremic and Virologically Suppressed HIV Infection Increases Age-Related Changes to Monocyte Activation Equivalent to 12 and 4 Years of Aging, Respectively. J Acquir Immune Defic Syndr, 2015. 69(1): p. 11–7. 10.1097/QAI.0000000000000559
    1. Nigam P., Kwa S., Velu V., and Amara R.R., Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection. J Immunol, 2011. 186(2): p. 745–53. 10.4049/jimmunol.1002807
    1. Noel N., Boufassa F., Lecuroux C., Saez-Cirion A., Bourgeois C., Dunyach-Remy C., Goujard C., Rouzioux C., Meyer L., Pancino G., Venet A., and Lambotte O., Elevated IP10 levels are associated with immune activation and low CD4(+) T-cell counts in HIV controller patients. Aids, 2014. 28(4): p. 467–76. 10.1097/QAD.0000000000000174
    1. Noel N., Lerolle N., Lecuroux C., Goujard C., Venet A., Saez-Cirion A., Avettand-Fenoel V., Meyer L., Boufassa F., and Lambotte O., Immunologic and Virologic Progression in HIV Controllers: The Role of Viral "Blips" and Immune Activation in the ANRS CO21 CODEX Study. PLoS One, 2015. 10(7): p. e0131922 10.1371/journal.pone.0131922
    1. Euler Z., van Gils M.J., Boeser-Nunnink B.D., Schuitemaker H., and van Manen D., Genome-wide association study on the development of cross-reactive neutralizing antibodies in HIV-1 infected individuals. PLoS One, 2013. 8(1): p. e54684 10.1371/journal.pone.0054684
    1. Legeai C., Vigouroux C., Souberbielle J.C., Bouchaud O., Boufassa F., Bastard J.P., Carlier R., Capeau J., Goujard C., Meyer L., and Viard J.P., Associations between 25-hydroxyvitamin D and immunologic, metabolic, inflammatory markers in treatment-naive HIV-infected persons: the ANRS CO9 <<COPANA>> cohort study. PLoS One, 2013. 8(9): p. e74868 10.1371/journal.pone.0074868
    1. Ghosn J., Pellegrin I., Goujard C., Deveau C., Viard J.P., Galimand J., Harzic M., Tamalet C., Meyer L., Rouzioux C., and Chaix M.L., HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time. Aids, 2006. 20(2): p. 159–70.
    1. Goujard C., Bonarek M., Meyer L., Bonnet F., Chaix M.L., Deveau C., Sinet M., Galimand J., Delfraissy J.F., Venet A., Rouzioux C., and Morlat P., CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients. Clin Infect Dis, 2006. 42(5): p. 709–15.
    1. Laanani M., Ghosn J., Essat A., Melard A., Seng R., Gousset M., Panjo H., Mortier E., Girard P.M., Goujard C., Meyer L., and Rouzioux C., Impact of the Timing of Initiation of Antiretroviral Therapy During Primary HIV-1 Infection on the Decay of Cell-Associated HIV-DNA. Clin Infect Dis, 2015. 60(11): p. 1715–21. 10.1093/cid/civ171
    1. Ngo-Giang-Huong N., Deveau C., Da Silva I., Pellegrin I., Venet A., Harzic M., Sinet M., Delfraissy J.F., Meyer L., Goujard C., and Rouzioux C., Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy. Aids, 2001. 15(6): p. 665–73.
    1. Cohen C.J., Crome S.Q., MacDonald K.G., Dai E.L., Mager D.L., and Levings M.K., Human Th1 and Th17 cells exhibit epigenetic stability at signature cytokine and transcription factor loci. J Immunol, 2011. 187(11): p. 5615–26. 10.4049/jimmunol.1101058
    1. Crome S.Q., Clive B., Wang A.Y., Kang C.Y., Chow V., Yu J., Lai A., Ghahary A., Broady R., and Levings M.K., Inflammatory effects of ex vivo human Th17 cells are suppressed by regulatory T cells. J Immunol, 2010. 185(6): p. 3199–208. 10.4049/jimmunol.1000557
    1. Rouzioux C., Melard A., and Avettand-Fenoel V., Quantification of total HIV1-DNA in peripheral blood mononuclear cells. Methods Mol Biol, 2014. 1087: p. 261–70. 10.1007/978-1-62703-670-2_21

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться