Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress

FASEB J. 2011 Jul;25(7):2211-20. doi: 10.1096/fj.10-175992. Epub 2011 Mar 22.

Abstract

Immunosuppressive lentivirus infections, including human, simian, and feline immunodeficiency viruses (HIV, SIV, and FIV, respectively), cause the acquired immunodeficiency syndrome (AIDS), frequently associated with AIDS enteropathy. Herein, we investigated the extent to which lentivirus infections affected mucosal integrity and intestinal permeability in conjunction with immune responses and activation of endoplasmic reticulum (ER) stress pathways. Duodenal biopsies from individuals with HIV/AIDS exhibited induction of IL-1β, CD3ε, HLA-DRA, spliced XBP-1(Xbp-1s), and CHOP expression compared to uninfected persons (P<0.05). Gut epithelial cells exposed to HIV-1 Vpr demonstrated elevated TNF-α, IL-1β, spliced Xbp-1s, and CHOP expression (P<0.05) together with calcium activation and disruption of epithelial cell monolayer permeability. In addition to reduced blood CD4(+) T lymphocyte levels, viral loads in the gut and plasma were high in FIV-infected animals (P<0.05). FIV-infected animals also exhibited a failure to gain weight and increased lactulose/mannitol ratios compared with uninfected animals (P<0.05). Proinflammatory and ER stress gene expression were activated in the ileum of FIV-infected animals (P<0.05), accompanied by intestinal epithelial damage with loss of epithelial cells and leukocyte infiltration of the lamina propria. Lentivirus infections cause gut inflammation and ensuing damage to intestinal epithelial cells, likely through induction of ER stress pathways, resulting in disruption of gut functional integrity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cats
  • Cell Line, Tumor
  • Duodenum / immunology
  • Duodenum / metabolism
  • Duodenum / virology
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism*
  • Enteritis / genetics*
  • Enteritis / immunology
  • Enteritis / virology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Female
  • Gene Expression
  • HIV Enteropathy / genetics*
  • HIV Enteropathy / immunology
  • HIV Enteropathy / virology
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / physiology
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / metabolism
  • HLA-DR alpha-Chains
  • Host-Pathogen Interactions
  • Humans
  • Immunodeficiency Virus, Feline / immunology
  • Immunodeficiency Virus, Feline / physiology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lentivirus Infections / genetics
  • Lentivirus Infections / immunology
  • Lentivirus Infections / virology
  • Pregnancy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Viral Load / immunology
  • vpr Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • CD3 Complex
  • CD3E protein, human
  • HLA-DR Antigens
  • HLA-DR alpha-Chains
  • Interleukin-1beta
  • vpr Gene Products, Human Immunodeficiency Virus
  • vpr protein, Human immunodeficiency virus 1