Infectious Microecology in Immunodeficiency Diseases

  • Jin Yang
  • Nanping Wu
Part of the Advanced Topics in Science and Technology in China book series (ATSTC)


Extensive research during the past two decades has provided new insight into the pathogenesis of the human immune deficiency virus-1 (HIV-1). With the emergence of the new theory of chronic immune activation, it has now become clear how the continuous T cell depletion occurred in HIV-1 progression. The improved understanding of mucosal immunity, especially in gut-associated lymphoid tissue (GALT), has led to a more rationale analysis of HIV-1 pathogenesis. With the role of microbiota looming on the horizon, new clues linking the gap between mucosal immunity dysfunction and immune activation depict an intricate continuum of the battle between the virus and the host. Altogether, the overview of the HIV-1 pathogenesis, in the view of the microecology presented here, further highlights the complexity of the mechanism of HIV-1, and sheds light on the novel strategy to control this notorious agent.


Human Immunodeficiency Virus Human Immunodeficiency Virus Infection Treg Cell Immune Activation Bacterial Vaginosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Claesson M J, Jeffery I B, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature, 2012, 488: 178–184.CrossRefPubMedGoogle Scholar
  2. [2]
    Lederberg J. Infectious history. Science, 2000, 288: 287–293.CrossRefPubMedGoogle Scholar
  3. [3]
    Wilcox C M, Saag M S. Gastrointestinal complications of HIV infection: Changing priorities in the HAART era. Gut, 2008, 57: 861–870.CrossRefPubMedGoogle Scholar
  4. [4]
    Anastassopoulou C G, Kostrikis L G. Viral correlates of HIV-1 disease. Curr HIV Res, 2005, 3: 113–132.CrossRefPubMedGoogle Scholar
  5. [5]
    Baden L R, Dolin R. The road to an effective HIV vaccine. N Engl J Med, 2012, 366: 1343–1344.CrossRefPubMedGoogle Scholar
  6. [6]
    Eberle J, Gurtler L. HIV types, groups, subtypes and recombinant forms: errors in replication, selection pressure and quasispecies. Intervirology, 2012, 55: 79–83.CrossRefPubMedGoogle Scholar
  7. [7]
    Smith S M. The pathogenesis of HIV infection: Stupid may not be so dumb after all. Retrovirology, 2006, 3: 60.PubMedCentralCrossRefPubMedGoogle Scholar
  8. [8]
    Durand CM, Blankson JN, Siliciano RF. Developing strategies for HIV-1 eradication. Trends Immunol, 2012, 33:554–562.PubMedCentralCrossRefPubMedGoogle Scholar
  9. [9]
    Amadori A, Zamarchi R, Chieco-Bianchi L. CD4: CD8 ratio and HIV infection: The “tap-and-drain” hypothesis. Immunology today, 1996, 17(9): 414–417.CrossRefPubMedGoogle Scholar
  10. [10]
    Lane H C. Pathogenesis of HIV infection: Total CD4+ T-cell pool, immune activation, and inflammation. Top HIV Med, 2010, 18(1): 2–6.PubMedGoogle Scholar
  11. [11]
    Grossman Z, Meier-Schellersheim M, Sousa AE, et al. CD4+ T-cell depletion in HIV infection: Are we closer to understanding the cause? Nat Med, 2002, 8(4): 319–323.CrossRefPubMedGoogle Scholar
  12. [12]
    Brenchley J M, Hill B J, Ambrozak D R, et al. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: Implications for HIV pathogenesis. J Virol, 2004, 78: 1160–1168.PubMedCentralCrossRefPubMedGoogle Scholar
  13. [13]
    Davey R T Jr, Bhat N, Yoder C, et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci USA, 1999, 96: 15109–15114.PubMedCentralCrossRefPubMedGoogle Scholar
  14. [14]
    Douek D C, Roederer M, Koup R A. Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med, 2009, 60: 471–484.PubMedCentralCrossRefPubMedGoogle Scholar
  15. [15]
    Silvestri G, Paiardini M, Pandrea I, et al. Understanding the benign nature of SIV infection in natural hosts. J Clin Invest, 2007, 117: 3148–3154.PubMedCentralCrossRefPubMedGoogle Scholar
  16. [16]
    Stein J H, Hsue P Y. Inflammation, immune activation, and CVD risk in individuals with HIV infection. JAMA, 2012, 308: 405–406.CrossRefPubMedGoogle Scholar
  17. [17]
    Brenchley J M, Price D A, Douek D C. HIV disease: Fallout from a mucosal catastrophe? Nat Immunol, 2006, 7: 235–239.CrossRefPubMedGoogle Scholar
  18. [18]
    Deeks S G, Hoh R, Grant R M, et al. CD4+ T cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapy. J Infect Dis, 2002, 185: 315–323.CrossRefPubMedGoogle Scholar
  19. [19]
    Kovacs J A, Lempicki R A, Sidorov I A, et al. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. J Exp Med, 2001, 194: 1731–1741.PubMedCentralCrossRefPubMedGoogle Scholar
  20. [20]
    Brenchley J M, Schacker T W, Ruff L E, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med, 2004, 200: 749–759.PubMedCentralCrossRefPubMedGoogle Scholar
  21. [21]
    Veazey R S, DeMaria M, Chalifoux L V, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science, 1998, 280: 427–431.CrossRefPubMedGoogle Scholar
  22. [22]
    Mehandru S, Tenner-Racz K, Racz P, et al. The gastrointestinal tract is critical to the pathogenesis of acute HIV-1 infection. J Allergy Clin Immunol, 2005, 116: 419–422.CrossRefPubMedGoogle Scholar
  23. [23]
    Kotler D P, Gaetz H P, Lange M, et al. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med, 1984, 101: 421–428.CrossRefPubMedGoogle Scholar
  24. [24]
    Smale S, Tibble J, Bjarnason I. Small intestinal permeability. Curr Opin Gastroenterol, 2000, 16: 134–139.CrossRefGoogle Scholar
  25. [25]
    Mowat A M. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol, 2003, 3: 331–341.CrossRefPubMedGoogle Scholar
  26. [26]
    Schieferdecker H L, Ullrich R, Hirseland H, et al. T cell differentiation antigens on lymphocytes in the human intestinal lamina propria. J Immunol, 1992, 149: 2816–2822.PubMedGoogle Scholar
  27. [27]
    Anton P A, Elliott J, Poles M A, et al. Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue. AIDS, 2000, 14: 1761–1765.CrossRefPubMedGoogle Scholar
  28. [28]
    Li Q, Duan L, Estes J D, et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature, 2005, 434: 1148–1152.PubMedGoogle Scholar
  29. [29]
    Paiardini M, Frank I, Pandrea I, et al. Mucosal immune dysfunction in AIDS pathogenesis. AIDS Rev, 2008, 10: 36–46.PubMedGoogle Scholar
  30. [30]
    Picker L J, Hagen S I, Lum R, et al. Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med, 2004, 200: 1299–1314.PubMedCentralCrossRefPubMedGoogle Scholar
  31. [31]
    Brenchley J M, Paiardini M, Knox K S, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood, 2008, 112: 2826–2835.PubMedCentralCrossRefPubMedGoogle Scholar
  32. [32]
    Bomsel M, Alfsen A. Entry of viruses through the epithelial barrier: Pathogenic trickery. Nature reviews Molecular cell biology, 2003, 4: 57–68.CrossRefPubMedGoogle Scholar
  33. [33]
    Cassol E, Malfeld S, Mahasha P, et al. Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J Infect Dis, 2010, 202: 723–733.CrossRefPubMedGoogle Scholar
  34. [34]
    Macpherson A J, Harris N L. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol, 2004, 4: 478–485.CrossRefPubMedGoogle Scholar
  35. [35]
    Brenchley J M, Price D A, Schacker T W, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med, 2006, 12: 1365–1371.CrossRefPubMedGoogle Scholar
  36. [36]
    Berg R D, Garlington A W. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun, 1979, 23: 403–411.PubMedCentralPubMedGoogle Scholar
  37. [37]
    Suffredini A F, Hochstein H D, McMahon FG. Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation of a new clinical lot of Escherichia coli O:113 endotoxin. J Infect Dis, 1999, 179: 1278–1282.CrossRefPubMedGoogle Scholar
  38. [38]
    Nowroozalizadeh S, Mansson F, da Silva Z, et al. Microbial translocation correlates with the severity of both HIV-1 and HIV-2 infections. J Infect Dis, 2010, 201: 1150–1154.CrossRefPubMedGoogle Scholar
  39. [39]
    Wallet M A, Rodriguez C A, Yin L, et al. Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. AIDS, 2010, 24: 1281–1290.PubMedCentralCrossRefPubMedGoogle Scholar
  40. [40]
    Ganusov V V, De Boer R J. Do most lymphocytes in humans really reside in the gut? Trends Immunol, 2007, 28: 514–518.CrossRefPubMedGoogle Scholar
  41. [41]
    Belmonte L, Olmos M, Fanin A, et al. The intestinal mucosa as a reservoir of HIV-1 infection after successful HAART. AIDS, 2007, 21: 2106–2108.CrossRefPubMedGoogle Scholar
  42. [42]
    Shen R, Smythies L E, Clements R H, et al. Dendritic cells transmit HIV-1 through human small intestinal mucosa. J Leukoc Biol, 2010, 87: 663–670.PubMedCentralCrossRefPubMedGoogle Scholar
  43. [43]
    Shattock R J, Moore J P. Inhibiting sexual transmission of HIV-1 infection. Nature reviews Microbiology, 2003, 1: 25–34.CrossRefPubMedGoogle Scholar
  44. [44]
    Ganor Y, Zhou Z, Tudor D, et al. Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates. Mucosal Immunol, 2010, 3: 506–522.CrossRefPubMedGoogle Scholar
  45. [45]
    Saba E, Grivel J C, Vanpouille C, et al. HIV-1 sexual transmission: Early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model. Mucosal Immunol, 2010, 3: 280–290.PubMedCentralCrossRefPubMedGoogle Scholar
  46. [46]
    Hladik F, Sakchalathorn P, Ballweber L, et al. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity, 2007, 26: 257–270.PubMedCentralCrossRefPubMedGoogle Scholar
  47. [47]
    Moodley P, Connolly C, Sturm AW. Interrelationships among human immunodeficiency virus type 1 infection, bacterial vaginosis, trichomoniasis, and the presence of yeasts. J Infect Dis, 2002, 185: 69–73.CrossRefPubMedGoogle Scholar
  48. [48]
    Knezevic A, Stepanovic S, Cupic M, et al. Reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women. Biomed Pharmacother, 2005, 59: 521–523.CrossRefPubMedGoogle Scholar
  49. [49]
    Frank D N, Manigart O, Leroy V, et al. Altered vaginal microbiota are associated with perinatal mother-to-child transmission of HIV in African women from Burkina Faso. J Acquir Immune Defic Syndr, 2012, 60: 299–306.CrossRefPubMedGoogle Scholar
  50. [50]
    Chung H, Kasper D L. Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Current opinion in immunology, 2010, 22: 455–460.CrossRefPubMedGoogle Scholar
  51. [51]
    Hooper L V, Macpherson A J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol, 2010, 10: 159–169.CrossRefPubMedGoogle Scholar
  52. [52]
    Fujimura K E, Slusher N A, Cabana M D, et al. Role of the gut microbiota in defining human health. Expert review of anti-infective therapy, 2010, 8: 435–454.PubMedCentralCrossRefPubMedGoogle Scholar
  53. [53] Sharma R, Young C, Neu J. Molecular modulation of intestinal epithelial barrier: Contribution of microbiota. Journal of biomedicine & biotechnology, 2010, 2010: aticle ID 305879.Google Scholar
  54. [54]
    Gori A, Tincati C, Rizzardini G, 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, 2008, 46: 757–758.PubMedCentralCrossRefPubMedGoogle Scholar
  55. [55]
    Kantor B, Ma H, Webster-Cyriaque J, et al. Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection. Proc Natl Acad Sci USA, 2009, 106: 18786–18791.PubMedCentralCrossRefPubMedGoogle Scholar
  56. [56]
    Dandekar S, George M D, Baumler A J. Th17 cells, HIV and the gut mucosal barrier. Curr Opin HIV AIDS, 2010, 5: 173–178.CrossRefPubMedGoogle Scholar
  57. [57]
    Round J L, Mazmanian S K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA, 2010, 107: 12204–12209.PubMedCentralCrossRefPubMedGoogle Scholar
  58. [58]
    Xing S, Fu J, Zhang Z, et al. Increased turnover of Foxp3 high regulatory T cells is associated with hyperactivation and disease progression of chronic HIV-1 infection. J Acquir Immune Defic Syndr, 2010, 54: 455–462.CrossRefPubMedGoogle Scholar
  59. [59]
    Ancuta P, Monteiro P, Sekaly RP. Th17 lineage commitment and HIV-1 pathogenesis. Curr Opin HIV AIDS, 2010, 5: 158–165.CrossRefPubMedGoogle Scholar
  60. [60]
    Milner J D, Sandler N G, Douek D C. Th17 cells, Job’s syndrome and HIV: opportunities for bacterial and fungal infections. Curr Opin HIV AIDS, 2010, 5: 179–183.PubMedCentralCrossRefPubMedGoogle Scholar
  61. [61]
    Macal M, Sankaran S, Chun T W, et al. Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses. Mucosal Immunol, 2008, 1: 475–488.CrossRefPubMedGoogle Scholar
  62. [62]
    Hunt P W. Th17, gut, and HIV: Therapeutic implications. Curr Opin HIV AIDS, 2010, 5: 189–193.PubMedCentralCrossRefPubMedGoogle Scholar
  63. [63]
    Hofer U, Speck R F. Disturbance of the gut-associated lymphoid tissue is associated with disease progression in chronic HIV infection. Semin Immunopathol, 2009, 31: 257–266.CrossRefPubMedGoogle Scholar
  64. [64] Schellenberg J J, Plummer F A. The microbiological context of hiv resistance: vaginal microbiota and mucosal inflammation at the viral point of entry. International journal of inflammation, 2012, 2012: article ID 131243.Google Scholar
  65. [65]
    Ramakrishna BS. Probiotic-induced changes in the intestinal epithelium: Implications in gastrointestinal disease. Trop Gastroenterol, 2009, 30: 76–85.PubMedGoogle Scholar
  66. [66]
    Cunningham-Rundles S, Ahrne S, Bengmark S, et al. Probiotics and immune response. Am J Gastroenterol, 2000, 95: S22–S25.CrossRefGoogle Scholar
  67. [67]
    Trois L, Cardoso E M, Miura E. Use of probiotics in HIV-infected children: A randomized double-blind controlled study. J Trop Pediatr, 2008, 54:19–24.CrossRefPubMedGoogle Scholar
  68. [68]
    Salminen M K, Tynkkynen S, Rautelin H, et al. The efficacy and safety of probiotic Lactobacillus rhamnosus GG on prolonged, noninfectious diarrhea in HIV Patients on antiretroviral therapy: A randomized, placebo-controlled, crossover study. HIV Clin Trials, 2004, 5:183–191.CrossRefPubMedGoogle Scholar
  69. [69]
    Rao S, Hu S, McHugh L, et al. Toward a live microbial microbicide for HIV: Commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl Acad Sci USA, 2005, 102: 11993–11998.PubMedCentralCrossRefPubMedGoogle Scholar
  70. [70]
    Bolton M, van der Straten A, Cohen CR. Probiotics: Potential to prevent HIV and sexually transmitted infections in women. Sex Transm Dis, 2008, 35: 214–225.CrossRefPubMedGoogle Scholar
  71. [71]
    Quigley EM. Prebiotics and probiotics; modifying and mining the microbiota. Pharmacol Res, 2010, 61: 213–218.CrossRefPubMedGoogle Scholar
  72. [72]
    van Loveren H, Sanz Y, Salminen S. Health claims in Europe: Probiotics and prebiotics as case examples. Annual review of food science and technology, 2012, 3: 247–261.CrossRefPubMedGoogle Scholar

Copyright information

© Zhejiang University Press, Hangzhou and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jin Yang
    • 1
    • 2
  • Nanping Wu
    • 1
    • 2
  1. 1.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, the First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesHangzhouChina

Personalised recommendations