Reversing Gut Damage in HIV Infection: Using Non-Human Primate Models to Instruct Clinical Research

EBioMedicine

Volumn 4, Issue , 2016, Pages 40-49

  Ponte, Rosalie ^a,b   Mehraj, Vikram ^a,b   Ghali, Peter ^b   Couëdel Courteille, Anne ^c,d,e   Cheynier, Rémi ^c,d,e   Routy, Jean Pierre ^a,b  

^a RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^c INSTITUT COCHIN   (France)

^d CNRS   (France)

^e UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

Gut barrier integrity; HIV; Interleukin 21; Interleukin 7; Microbial translocation; SIV

Indexed keywords

INTERLEUKIN 21; INTERLEUKIN 7;

ADAPTIVE IMMUNITY; ANTIRETROVIRAL THERAPY; CD8+ T LYMPHOCYTE; CELLULAR DISTRIBUTION; CHLOROCEBUS AETHIOPS; DISEASE COURSE; FLOW CYTOMETRY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOHISTOCHEMISTRY; MICROENVIRONMENT; MUCOSAL IMMUNITY; NONHUMAN; PLASMACYTOID DENDRITIC CELL; PRIORITY JOURNAL; REVIEW; AIDS-RELATED OPPORTUNISTIC INFECTIONS; ANIMAL; HUMAN; IMMUNOLOGY; INNATE IMMUNITY; INTESTINAL DISEASES; INTESTINE MUCOSA; MACACA; METABOLISM; MICROBIOLOGY; MICROFLORA; PATHOLOGY; PRECLINICAL STUDY;

AIDS-RELATED OPPORTUNISTIC INFECTIONS; ANIMALS; DRUG EVALUATION, PRECLINICAL; HUMANS; IMMUNITY, INNATE; INTESTINAL DISEASES; INTESTINAL MUCOSA; MACACA; MICROBIOTA;

EID: 84957092023     PISSN: None     EISSN: 23523964     Source Type: Journal    
DOI: 10.1016/j.ebiom.2016.01.028     Document Type: Review

References (98)

1. Allers, K., et al. Macrophages accumulate in the gut mucosa of untreated HIV-infected patients. J. Infect. Dis. 209:5 (2014), 739–748.
2. Allers, K., et al. The effect of timing of antiretroviral therapy on CD4 + T-cell reconstitution in the intestine of HIV-infected patients. Mucosal Immunol., 2015, 1–10.
3. Artis, D., Spits, H., The biology of innate lymphoid cells. Nature 517:7534 (2015), 293–301.
4. Asmuth, D.M., et al. Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy. AIDS (London, England) 27:14 (2013), 2207–2217.
5. Aujla, S.J., Kolls, J.K., IL-22: a critical mediator in mucosal host defense. J. Mol. Med. (Berl., Ger.) 87:5 (2009), 451–454.
6. Beq, S., et al. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J. Immunol. (Baltimore, Md.: 1950) 176:2 (2006), 914–922.
7. Beq, S., et al. Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques. Blood 114:4 (2009), 816–825.
8. Boasso, A., et al. Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques. J. Immunol. 182:7 (2009), 4313–4320.
9. Brandtzaeg, P., et al. Terminology: nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol. 1:1 (2008), 31–37.
10. Brenchley, J.M., Mucosal immunity in human and simian immunodeficiency lentivirus infections. Mucosal Immunol. 6:4 (2013), 657–665.
11. Brenchley, J.M., et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12:12 (2006), 1365–1371.
12. Bruel, T., et al. Plasmacytoid dendritic cell dynamics tune interferon-alfa production in SIV-infected cynomolgus macaques. PLoS Pathog., 10(1), 2014, e1003915.
13. Byrareddy, S.N., et al. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection. Nat. Med. 20:12 (2014), 1397–1400.
14. Cao, W., Mehraj, V., Trottier, B., et al. Early initiation rather than prolonged duration of antiretroviral therapy in HIV infection contributes to the normalization of CD8 T-cell counts. Clin. Infect. Dis., 2015.
15. Cao, W., Mehraj, V., Vyboh, K., et al. Antiretroviral therapy in primary HIV-1 infection: influences on immune activation and gut mucosal barrier dysfunction. AIDS Rev. 17:3 (2015), 135–146.
16. Cassol, E., et al. CD14 + macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide. BMC Infect. Dis., 2015, 1–13.
17. Chahroudi, A., et al. Natural SIV hosts: showing AIDS the door. Science 335:6073 (2012), 1188–1193.
18. Choi, Y.K., et al. Productive infection of dendritic cells by simian immunodeficiency virus in macaque intestinal tissues. J. Pathol. 201:4 (2003), 616–628.
19. Cimbro, R., et al. IL-7 induces expression and activation of integrin 4 7 promoting naive T-cell homing to the intestinal mucosa. Blood 120:13 (2012), 2610–2619.
20. Clay, C.C., et al. Distinct chemokine triggers and in vivo migratory paths of fluorescein dye-labeled T lymphocytes in acutely simian immunodeficiency virus SIVmac251-infected and uninfected macaques. J. Virol. 79:21 (2005), 13759–13768.
21. Couëdel-Courteille, A., et al. Delayed viral replication and CD4(+) T cell depletion in the rectosigmoid mucosa of macaques during primary rectal SIV infection. Virology 316:2 (2003), 290–301.
22. DaFonseca, S., et al. Impaired Th17 polarization of phenotypically naive CD4(+) T-cells during chronic HIV-1 infection and potential restoration with early ART. Retrovirology, 12, 2015, 38.
23. Dillon, S.M., et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 7:4 (2014), 983–994.
24. Dyavar Shetty, R., et al. PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques. J. Clin. Investig. 122:5 (2012), 1712–1716.
25. Eberl, G., et al. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science, 348(6237), 2015, aaa6566.
26. Elbim, C., et al. Early divergence in neutrophil apoptosis between pathogenic and nonpathogenic simian immunodeficiency virus infections of nonhuman primates. J. Immunol. 181:12 (2008), 8613–8623.
27. Epple, H.-J., et al. Mucosal but not peripheral FOXP3 + regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108:9 (2006), 3072–3078.
28. Estes, J.D., et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. Trkola, A., (eds.) PLoS Pathogens, 6(8), 2010, e1001052.
29. Favre, D., et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. Luban, J., (eds.) PLoS Pathogens, 5(2), 2009, e1000295.
30. Glavan, T.W., et al. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection. Mucosal Immunol, 2015.
31. Gori, A., et al. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis. J. Clin. Microbiol. 46:2 (2008), 757–758.
32. Handley, S.A., et al. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 151:2 (2012), 253–266.
33. Hao, X.P., et al. Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. Nat. Commun. 6 (2015), 1–12.
34. Hensley-McBain T., et al. Lack of neutrophil recruitment to mucosal sites after SIV infection is associated with inflammation and viremia. HIV Research for Prevention conference, 2014, 12.05.
35. Hirao, L.A., et al. Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption. Silvestri, G., (eds.) PLoS Pathogens, 10(8), 2014, e1004311.
36. Ho, T.H., et al. Review article: the intersection of mucosal pathophysiology in HIV and inflammatory bowel disease, and its implications for therapy. Aliment. Pharmacol. Ther. 40:10 (2014), 1171–1186.
37. Jenabian, M.-A., et al. Immunosuppressive tryptophan catabolism and gut mucosal dysfunction following early HIV infection. J. Infect. Dis. 212:3 (2015), 355–366.
38. Jenq, R.R., et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J. Exp. Med. 209:5 (2012), 903–911.
39. Kenway-Lynch, C.S., et al. Dynamics of cytokine/chemokine responses in intestinal CD4 + and CD8 + T cells during acute simian immunodeficiency virus infection. J. Virol. 87:21 (2013), 11916–11923.
40. Klase, Z., et al. Dysbiotic bacteria translocate in progressive SIV infection. Mucosal Immunol. 8:5 (2015), 1009–1020.
41. Klatt, N.R., et al. Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection. Mucosal Immunol. 3:4 (2010), 387–398.
42. Klatt, N.R., et al. Loss of mucosal CD103 + DCs and IL-17 + and IL-22 + lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol. 5:6 (2012), 646–657.
43. Klatt, N.R., et al. Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques. J. Clin. Investig. 123:2 (2013), 903–907.
44. Kotler, D.P., et al. Enteropathy associated with the acquired immunodeficiency syndrome. Ann. Intern. Med. 101:4 (1984), 421–428.
45. Kristoff, J., et al. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication. J. Clin. Investig. 124:6 (2014), 2802–2806.
46. Lee, S.-Y., et al. Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/Treg balance. Unutmaz, D., (eds.) PLoS ONE, 10(9), 2015, e0135858.
47. Levy, Y., et al. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin. Infect. Dis. 55:2 (2012), 291–300.
48. Li, Q., et al. Peak SIV replication in resting memory CD4 + T cells depletes gut lamina propria CD4 + T cells. Nature 434:7037 (2005), 1148–1152.
49. Li, Q., et al. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J. Infect. Dis. 197:3 (2008), 420–429.
50. Li, Q., et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature 458:7241 (2009), 1034–1038.
51. Li, H., et al. Hypercytotoxicity and rapid loss of NKp44 + innate lymphoid cells during acute SIV infection. Silvestri, G., (eds.) PLoS Pathogens, 10(12), 2014, e1004551.
52. Li, H., et al. Bone marrow-imprinted gut-homing of plasmacytoid dendritic cells (pDCs) in acute simian immunodeficiency virus infection results in massive accumulation of hyperfunctional CD4 + pDCs in the mucosae. J. Infect. Dis. 211:11 (2015), 1717–1725.
53. Lozupone, C.A., et al. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe 14:3 (2013), 329–339.
54. Marchetti, G., Tincati, C., Silvestri, G., Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin. Microbiol. Rev. 26:1 (2013), 2–18.
55. Mattapallil, J.J., et al. Massive infection and loss of memory CD4 + T cells in multiple tissues during acute SIV infection. Nature 434:7037 (2005), 1093–1097.
56. Mehandru, S., et al. Primary HIV-1 infection is associated with preferential depletion of CD4 + T lymphocytes from effector sites in the gastrointestinal tract. J. Exp. Med. 200:6 (2004), 761–770.
57. Micci, L., et al. Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques. J. Clin. Investig., 2015.
58. Mohan, M., et al. Focused examination of the intestinal epithelium reveals transcriptional signatures consistent with disturbances in enterocyte maturation and differentiation during the course of SIV infection. PLoS ONE, 8(4), 2013, e60122.
59. Mudd, J.C., Lederman, M.M., CD8 T cell persistence in treated HIV infection. Curr. Opin. HIV AIDS 9:5 (2014), 500–505.
60. Nigam, P., et al. Expansion of FOXP3 + CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control. J. Immunol. 184:4 (2010), 1690–1701.
61. Nigam, P., et al. Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection. J. Immunol. 186:2 (2011), 745–753.
62. Nowak, P., et al. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS (London, England), 2015.
63. Ortiz, A.M., et al. IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. Mucosal Immunol., 2015.
64. Pallikkuth, S., et al. Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21. Douek, D.C., (eds.) PLoS Pathogens, 9(7), 2013, e1003471.
65. Pan, D., et al. Lack of interleukin-10-mediated anti-inflammatory signals and upregulated interferon gamma production are linked to increased intestinal epithelial cell apoptosis in pathogenic simian immunodeficiency virus infection. J. Virol. 88:22 (2014), 13015–13028.
66. Pandrea, I., Apetrei, C., Where the wild things are: pathogenesis of SIV infection in African nonhuman primate hosts. Curr. HIV/AIDS Rep. 7:1 (2010), 28–36.
67. Ponte, R., Perturbations de l'homéostasie lymphocytaire T chez le macaque rhésus chinois en phase aiguë d'infection par le SIVmac251. (Ph.D thesis), 2014, Paris Descartes University of Medicine (Available from: Theses.fr. [9 october 2013]).
68. Quigley, M.F., et al. Perforin expression in the gastrointestinal mucosa is limited to acute simian immunodeficiency virus infection. J. Virol. 80:6 (2006), 3083–3087.
69. Reeves, R.K., et al. Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44 + mucosal NK cells during SIV infection. Blood 118:12 (2011), 3321–3330.
70. Reeves, R.K., et al. SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa. J. Infect. Dis. 206:9 (2012), 1462–1468.
71. Reynolds, L.A., Finlay, B.B., Maizels, R.M., Cohabitation in the intestine: interactions among helminth parasites, bacterial microbiota, and host immunity. J. Immunol. 195:9 (2015), 4059–4066.
72. Rodgers, V.D., Fassett, R., Kagnoff, M.F., Abnormalities in intestinal mucosal T cells in homosexual populations including those with the lymphadenopathy syndrome and acquired immunodeficiency syndrome. Gastroenterology 90:3 (1986), 552–558.
73. Routy, J.-P., et al. Clinical relevance of kynurenine pathway in HIV/AIDS: an immune checkpoint at the crossroads of metabolism and inflammation. AIDS Rev. 17:2 (2015), 96–106.
74. Sandler, N.G., et al. Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol levels in individuals with untreated HIV infection. J. Infect. Dis. 210:10 (2014), 1549–1554.
75. Schultheiss, T., Stahl-Hennig, C., Correlation between CD4 + T-cell loss and gag-specific T cells in different intestinal sites of chronically SIV-infected rhesus monkeys. AIDS (London, England) 25:4 (2011), 429–433.
76. Sereti, I., et al. Decreases in colonic and systemic inflammation in chronic HIV infection after IL-7 administration. Silvestri, G., (eds.) PLoS Pathogens, 10(1), 2014, e1003890.
77. Shaw, J.M., et al. Increased frequency of regulatory T cells accompanies increased immune activation in rectal mucosae of HIV-positive noncontrollers. J. Virol. 85:21 (2011), 11422–11434.
78. Shen, R., et al. Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection. J. Virol. 83:7 (2009), 3258–3267.
79. Smith, P.D., Ochsenbauer-Jambor, C., Smythies, L.E., Intestinal macrophages: unique effector cells of the innate immune system. Immunol. Rev. 206 (2005), 149–159.
80. Smith, P.D., et al. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol. 4:1 (2010), 31–42.
81. Somsouk, M., et al. Gut epithelial barrier and systemic inflammation during chronic HIV infection. AIDS (London, England) 29:1 (2015), 43–51.
82. Spits, H., et al. Innate lymphoid cells—a proposal for uniform nomenclature. Nat. Rev. Immunol. 13:2 (2013), 145–149.
83. Tabb, B., et al. Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection. J. Infect. Dis. 207:6 (2013), 880–892.
84. Trautmann, L., et al. Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction. Nat. Med. 12:10 (2006), 1198–1202.
85. Veazey, R.S., et al., Gastrointestinal tract as a major site of CD4 + T cell depletion and viral replication in SIV infection. Science 280:5362 (1998), 427–431.
86. Veazey, R.S., et al. Dynamics of CCR5 expression by CD4(+) T cells in lymphoid tissues during simian immunodeficiency virus infection. J. Virol. 74:23 (2000), 11001–11007.
87. Velu, V., et al. Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options. Retrovirology, 12, 2015, 14.
88. Vujkovic-Cvijin, I., et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci. Transl. Med., 5(193), 2013, 193ra91.
89. Vujkovic-Cvijin, I., et al. Gut-resident Lactobacillus abundance associates with IDO1 inhibition and Th17 dynamics in SIV-infected macaques. Cell Rep., 2015, 1–10.
90. Vyboh, K., et al. HIV and the gut microbiota, partners in crime: breaking the vicious cycle to unearth new therapeutic targets. J. Immunol. Res., 2015, 1–9.
91. Wang, X., et al. Divergent kinetics of proliferating T cell subsets in simian immunodeficiency virus (SIV) infection: SIV eliminates the “first responder” CD4 + T cells in primary infection. J. Virol. 87:12 (2013), 7032–7038.
92. Xu, H., Wang, X., Veazey, R.S., Th17 cells coordinate with Th22 cells in maintaining homeostasis of intestinal tissues and both are depleted in SIV-infected macaques. J. AIDS Clin. Res., 05(05), 2014.
93. Xu, H., et al. IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol. 5:6 (2012), 658–669.
94. Xu, H., et al. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques. FASEB J. 29:12 (2015), 5072–5080.
95. Younas, M., et al. Immune activation in the course of HIV-1 infection: causes, phenotypes and persistence under therapy. HIV Med., 2015.
96. Zhang, Z., et al. Plasmacytoid dendritic cells promote HIV-1–induced group 3 innate lymphoid cell depletion. J. Clin. Investig. 125:9 (2015), 3692–3703.
97. Zhou, Z., et al. HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells. Silvestri, G., (eds.) PLoS Pathogens, 7(6), 2011, e1002100.
98. Zhou, Y., et al. SIV infection of rhesus macaques of Chinese origin: a suitable model for HIV infection in humans. Retrovirology, 10(1), 2013, 1-1.