title: Microbial products trigger autoimmune ocular inflammation.
abstract: OBJECTIVE
  Microbial products stimulate the immune system by interacting with Toll-like receptors (TLR) on antigen-presenting cells. This study examined the hypothesis that microbial products, which function as TLR ligands, are playing a major role in triggering pathogenic autoimmunity.
  
  
  METHODS
  An experimental system was developed in which microbial TLR ligands were tested in vivo for their capacity to stimulate naïve CD4 cells specific against hen egg lysozyme (HEL) to become effector cells capable of inducing inflammation in eyes in which HEL is expressed. The ligands' mode of action was analyzed by determining their effects on the proliferation, acquisition of tissue-invading capacity, i.e. elevated CD49d and decreased CD62L expression, and production of interferon-gamma by the HEL-specific cells.
  
  
  RESULTS
  All the 7 tested TLR ligands triggered ocular inflammation in the experimental system used here, with pertussis toxin surpassing all other ligands in its activities. A correlation was found between the capacity of the ligands to trigger pathogenic immunity and to stimulate the proliferation, modification of cell surface and interferon-gamma production by T cells.
  
  
  CONCLUSIONS
  This study provides direct evidence to support the notion that microbial products are capable of triggering pathogenic autoimmunity.
authors.affiliation: Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1857, USA.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Fujimoto
authors.forename: Guangpu
authors.initials: G
authors.lastname: Shi
authors.forename: Igal
authors.initials: I
authors.lastname: Gery
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001419:Bacteria / Q000378:metabolism*; D001427:Bacterial Toxins / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D039421:Integrin alpha2 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000633:toxicity*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens; D001427:Bacterial Toxins; D039421:Integrin alpha2; D008024:Ligands; D011135:Polysaccharides, Bacterial; D051193:Toll-Like Receptors; D019041:L-Selectin; D007371:Interferon-gamma; C421864:hen egg lysozyme; D009113:Muramidase