Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression

Journal of Infectious Diseases

Volumn 214, Issue , 2016, Pages S58-S66

  Mudd, Joseph C ^a   Brenchley, Jason M ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

cART; gastrointestinal tract; HIV 1 pathognesis; microbiome; probiotics; residual inflammation; Th17

Indexed keywords

ANTIRETROVIRUS AGENT; INTERLEUKIN 17; INTERLEUKIN 22; PROBIOTIC AGENT; RIFAXIMIN;

ARTICLE; CD4+ T LYMPHOCYTE; COMMENSAL; CYTOKINE PRODUCTION; DIGESTIVE SYSTEM FUNCTION DISORDER; DISEASE ASSOCIATION; DYSBIOSIS; GUT MUCOSAL BARRIER DYSFUNCTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOCOMPETENT CELL; INTESTINE EPITHELIUM CELL; INTESTINE FLORA; LACTOBACILLUS; MICROBIAL DYSBIOSIS; MORTALITY; NONHUMAN; PRIORITY JOURNAL; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; VIRUS REPLICATION; VIRUS TRANSMISSION; ANIMAL; DISEASE COURSE; DRUG EFFECTS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; INTESTINE MUCOSA; MICROBIOLOGY; MUCOSAL IMMUNITY; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SIMIAN IMMUNODEFICIENCY VIRUS; VIROLOGY;

ANIMALS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; DISEASE PROGRESSION; DYSBIOSIS; GASTROINTESTINAL MICROBIOME; HIV INFECTIONS; HIV-1; HUMANS; IMMUNITY, MUCOSAL; INTESTINAL MUCOSA; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS;

EID: 84990929557     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiw258     Document Type: Article

References (98)

1. Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999; 179:859-70.
2. Hunt PW, Brenchley J, Sinclair E, et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis 2008; 197:126-33.
3. Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993; 328:327-35.
4. Lederman MM, Funderburg NT, Sekaly RP, Klatt NR, Hunt PW. Residual immune dysregulation syndrome in treated HIV infection. Adv Immunol 2013; 119:51-83.
5. Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004; 200:749-59.
6. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12:1365-71.
7. Estes JD, Harris LD, Klatt NR, et al. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog 2010; 6:e1001052.
8. Mehandru S, Poles MA, Tenner-Racz K, et al. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Med 2006; 3:e484.
9. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep 2006; 7:688-93.
10. Reyes A, Haynes M, Hanson N, et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 2010; 466:334-8.
11. Underhill DM, Iliev ID. The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol 2014; 14:405-16.
12. Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science 2006; 312:1355-9.
13. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9:799-809.
14. Aujla SJ, Kolls JK. IL-22: a critical mediator in mucosal host defense. J Mol Med (Berl) 2009; 87:451-4.
15. Cella M, Fuchs A, Vermi W, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 2009; 457:722-5.
16. Klatt NR, Estes JD, Sun X, et al. Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol 2012; 5:646-57.
17. Sugimoto K, Ogawa A, Mizoguchi E, et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 2008; 118:534-44.
18. Rodgers VD, Fassett R, Kagnoff MF. Abnormalities in intestinal mucosal T cells in homosexual populations including those with the lymphadenopathy syndrome and acquired immunodeficiency syndrome. Gastroenterology 1986; 90:552-8.
19. Li Q, Duan L, Estes JD, et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005; 434:1148-52.
20. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005; 434:1093-7.
21. Whitney JB, Hill AL, Sanisetty S, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature 2014; 512:74-7.
22. Barouch DH, Ghneim K, Bosche WJ, et al. Rapid inflammasome activation following mucosal SIV infection of Rhesus ronkeys. Cell 2016; 165:656-67.
23. Gordon SN, Klatt NR, Bosinger SE, et al. Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol 2007; 179:3026-34.
24. Kovacs SB, Sheikh V, Thompson WL, et al. T-cell depletion in the colonic mucosa of patients with idiopathic CD4+ lymphopenia. J Infect Dis 2015; 212:1579-87.
25. Schuetz A, Deleage C, Sereti I, et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog 2014; 10:e1004543.
26. Brenchley JM. Mucosal immunity in human and simian immunodeficiency lentivirus infections. Mucosal Immunol 2013; 6:657-65.
27. Ryan ES, Micci L, Fromentin R, et al. Loss of function of intestinal IL-17 and IL-22 producing cells contributes to inflammation and viral persistence in SIV-infected rhesus macaques. PLoS Pathog 2016; 12:e1005412.
28. Monteiro P, Gosselin A, Wacleche VS, et al. Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin beta7. J Immunol 2011; 186:4618-30.
29. El Hed A, Khaitan A, Kozhaya L, et al. Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection. J Infect Dis 2010; 201:843-54.
30. Alvarez Y, Tuen M, Shen G, et al. Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands. J Virol 2013; 87:10843-54.
31. Xu H, Wang X, Liu DX, Moroney-Rasmussen T, Lackner AA, Veazey RS. IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol 2012; 5:658-69.
32. Li H, Richert-Spuhler LE, Evans TI, et al. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection. PLoS Pathog 2014; 10:e1004551.
33. Kloverpris HN, Kazer SW, Mjosberg J, et al. innate lymphoid cells are depleted irreversibly during acute HIV-1 infection in the absence of viral suppression. Immunity 2016; 44:391-405.
34. Cosgrove C, Ussher JE, Rauch A, et al. Early and nonreversible decrease of CD161++/MAIT cells in HIV infection. Blood 2013; 121:951-61.
35. Vinton C, Wu F, Rossjohn J, et al. Mucosa-Associated Invariant T Cells Are Systemically Depleted in Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Virol 2016; 90:4520-9.
36. Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008; 112:2826-35.
37. Zhang Z, Cheng L, Zhao J, et al. Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion. J Clin Invest 2015; 125:3692-703.
38. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4:762-74.
39. Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med 2010; 2:32ra6.
40. Kotler DP, Gaetz HP, Lange M, Klein EB, Holt PR. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101:421-8.
41. Bjarnason I, Sharpstone DR, Francis N, et al. Intestinal inflammation, ileal structure and function in HIV. AIDS 1996; 10:1385-91.
42. Nazli A, Chan O, Dobson-Belaire WN, et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog 2010; 6:e1000852.
43. Mohan M, Aye PP, Borda JT, Alvarez X, Lackner AA. Gastrointestinal disease in simian immunodeficiency virus-infected rhesus macaques is characterized by proinflammatory dysregulation of the interleukin-6-Janus kinase/signal transducer and activator of transcription3 pathway. Am J Pathol 2007; 171:1952-65.
44. Schulbin H, Bode H, Stocker H, et al. Cytokine expression in the colonic mucosa of human immunodeficiency virus-infected individuals before and during 9 months of antiretroviral therapy. Antimicrob Agents Chemother 2008; 52:3377-84.
45. KimWK, Sun Y, Do H, et al.Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage. J Leukoc Biol 2010; 87:557-67.
46. Ancuta P, Kamat A, Kunstman KJ, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One 2008; 3: e2516.
47. Hao XP, Lucero CM, Turkbey B, et al. Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection. Nat Commun 2015; 6:8020.
48. Funderburg NT, Stubblefield Park SR, Sung HC, et al. Circulating CD4(+) and CD8(+) T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation. Immunology 2013; 140:87-97.
49. Pasternak BA, D'Mello S, Jurickova II, et al. Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohn's disease and murine colitis. Inflamm Bowel Dis 2010; 16:856-69.
50. Siliciano JD, Siliciano RF. Biomarkers of HIV replication. Curr Opin HIV AIDS 2010; 5:491-7.
51. Duprez DA, Kuller LH, Tracy R, et al. Lipoprotein particle subclasses, cardiovascular disease and HIV infection. Atherosclerosis 2009; 207:524-9.
52. Lederman MM, Calabrese L, Funderburg NT, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis 2011; 204:1217-26.
53. Miao YM, Hayes PJ, Gotch FM, Barrett MC, Francis ND, Gazzard BG. Elevated mucosal addressin cell adhesion molecule-1 expression in acquired immunodeficiency syndrome is maintained during antiretroviral therapy by intestinal pathogens and coincides with increased duodenal CD4T cell densities. J Infect Dis 2002; 185:1043-50.
54. Guadalupe M, Sankaran S, George MD, et al. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. J Virol 2006; 80:8236-47.
55. Chung CY, Alden SL, Funderburg NT, Fu P, Levine AD. Progressive proximal-todistal reduction in expression of the tight junction complex in colonic epithelium of virally-suppressed HIV+ individuals. PLoS Pathog 2014; 10:e1004198.
56. Serrano-Villar S, Sainz T, Ma ZM, et al. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial. PLoS Pathog 2016; 12: e1005381.
57. Sandler NG,Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011; 203:780-90.
58. Hunt PW, Shive C, Clagett B, Funderburg N, Nattat MV, et al. Gut epithelial barrier dysfunction, inflammation, and coagulation predict higher mortality during treated HIV/AIDS [abstract 278]. In: Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 2012.
59. Tenorio A, Zheng E, Bosch R, et al. Soluble markers of inflammation and coagulation, but not T-cell activation, predict nonAIDS-defining events during suppressive antiretroviral therapy [abstract 790]. In: Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Atlanta, Georgia, 2013.
60. Tenorio AR, Zheng Y, Bosch RJ, et al. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis 2014; 210:1248-59.
61. Zhang ZQ, Notermans DW, Sedgewick G, et al. Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection. Proc Natl Acad Sci USA 1998; 95:1154-9.
62. Estes J, Baker JV, Brenchley JM, et al. Collagen deposition limits immune reconstitution in the gut. J Infect Dis 2008; 198:456-64.
63. Kim CJ, McKinnon LR, Kovacs C, et al. Mucosal Th17 cell function is altered during HIV infection and is an independent predictor of systemic immune activation. J Immunol 2013; 191:2164-73.
64. Chun TW, Nickle DC, Justement JS, et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 2008; 197:714-20.
65. Tilg H, Moschen A, Kaser A. Mode of function of biological anti-TNF agents in the treatment of inflammatory bowel diseases. Expert Opin Biol Ther 2007; 7:1051-9.
66. Hold GL, Smith M, Grange C,Watt ER, El-Omar EM, Mukhopadhya I. Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? World J Gastroenterol 2014; 20:1192-210.
67. Vujkovic-Cvijin I, Dunham RM, Iwai S, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med 2013; 5:193ra91.
68. Dillon SM, Lee EJ, Kotter CV, et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol 2014; 7:983-94.
69. Mutlu EA, Keshavarzian A, Losurdo J, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog 2014; 10:e1003829.
70. Lozupone CA, Li M, Campbell TB, et al. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe 2013; 14:329-39.
71. Vazquez-Castellanos JF, Serrano-Villar S, Latorre A, et al. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals. Mucosal Immunol 2015; 8:760-72.
72. Yu G, Fadrosh D, Ma B, Ravel J, Goedert JJ. Anal microbiota profiles in HIV-positive and HIV-negative MSM. AIDS 2014; 28:753-60.
73. Noguera-Julian M, Rocafort M, Guillen Y, et al. Gut microbiota linked to sexual preference and HIV infection. EBioMedicine 2016; 5:135-46.
74. Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature 2013; 500:541-6.
75. Manichanh C, Borruel N, Casellas F, Guarner F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol 2012; 9:599-608.
76. Nowak P, Troseid M, Avershina E, et al. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS 2015; 29:2409-18.
77. McKenna P, Hoffmann C, Minkah N, et al. The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS Pathog 2008; 4:e20.
78. Handley SA, Thackray LB, Zhao G, et al. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 2012; 151:253-66.
79. Klatt NR, Canary LA, Sun X, et al. Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques. J Clin Invest 2013; 123:903-7.
80. Monaco CL, Gootenberg DB, Zhao G, et al. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome. Cell Host Microbe 2016; 19:311-22.
81. Klase Z, Ortiz A, Deleage C, et al. Dysbiotic bacteria translocate in progressive SIV infection. Mucosal Immunol 2015; 8:1009-20.
82. Kartalija M, Sande MA. Diarrhea and AIDS in the era of highly active antiretroviral therapy. Clin Infect Dis 1999; 28:701-5; quiz 6-7.
83. Kok A, Hocqueloux L, Hocini H, et al. Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients. Mucosal Immunol 2015; 8:127-40.
84. Kristoff J, Haret-Richter G, Ma D, et al. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication. J Clin Invest 2014; 124:2802-6.
85. Sandler NG, Zhang X, Bosch RJ, 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 2014; 210:1549-54.
86. Somsouk M, Dunham RM, Cohen M, et al. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial. PLoS One 2014; 9:e116306.
87. Tenorio AR, Chan ES, Bosch RJ, et al. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy-ACTG A5286. J Infect Dis 2015; 211:780-90.
88. Pandrea I, Xu C, Stock JL, et al. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques. PLoS Pathog 2016; 12:e1005384.
89. Stiksrud B, Nowak P, Nwosu FC, et al. Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART. J Acquir Immune Defic Syndr 2015; 70:329-37.
90. Villar-Garcia J, Hernandez JJ, Guerri-Fernandez R, et al. Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial. J Acquir Immune Defic Syndr 2015; 68:256-63.
91. d'Ettorre G, Ceccarelli G, Giustini N, et al. Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the "Probio-HIV" Clinical Trial. PLoS One 2015; 10:e0137200.
92. Gori A, Rizzardini G, Van't Land B, et al. Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial. Mucosal Immunol 2011; 4:554-63.
93. Gonzalez-Hernandez LA, Jave-Suarez LF, Fafutis-Morris M, et al. Synbiotic therapy decreases microbial translocation and inflammation and improves immunological status in HIV-infected patients: a double-blind randomized controlled pilot trial. Nutr J 2012; 11:90.
94. Li SS, Zhu A, Benes V, et al. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science 2016; 352:586-9.
95. Somsouk M, Vujkovic-Cvijin I, Pao M, Hunt PW, Lynch SV, Mccune JM. Fecal microbial transplantation: safety and engraftment during treated HIV infection [abstract 264]. In: Program and Abstracts from the 23rd Conference on Retroviruses and Opportunistic Infections, Boston, Massachusetts, 2016.
96. Hensley-McBain T, Zevin AS, Manuzak J, et al. Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques. J Virol 2016; 90:4981-9.
97. Micci L, Ryan ES, Fromentin R, et al. Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques. J Clin Invest 2015; 125:4497-513.
98. Thiebaut R, Jarne A, Routy JP, et al. Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected PatientsWith Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies. Clin Infect Dis 2016; 62:1178-85.