Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

The effect of microbiome/Toll-like receptor interactions on susceptibility to type 1 diabetes (#23)

Margaret A Jordan 1 , Dragana Stanley 2 , Robert J Moore 3 , Sumaira Hasnain 4 , Michael McGuckin 4 , Tim Butler 1 , Shahead Chowdhury 1 , Roby Jose 1 , Erik Biros 1 , Marie Du Toit 1 , Karinne Law 1 , Socorro Miranda-Hernandez 1 , Benjamin Crowley 1 , Alan G Baxter 1
  1. Comparative Genomics Centre, Townsville, QLD, Australia
  2. School of Medical and Applied Sciences, Central Queensland University, Rockhampton, QLD 4702, Australia
  3. Australian Animal Health Laboratory, CSIRO, Geelong, Victoria 3220, Australia
  4. Mater Research, Translational Research Institute, Woolloongabba, QLD 4102, Australia

The role of TLR in autoimmunity was studied by crossing TLR1,2,4,6,9 and MyD88 targeted deficiency mutations to the type 1 diabetes (T1D)-prone NOD mouse strain. While NOD.Tlr9-/- and NOD.Tlr6-/- mice were unaffected, T1D in NOD.Tlr4-/- and NOD.Tlr1-/- mice was exacerbated and that in NOD.Myd88-/- and NOD.Tlr2-/- mice ameliorated. The intestinal microbiomes of NOD wild-type (WT), NOD.Tlr1-/-, NOD.Tlr2-/- and NOD.Tlr4-/- mice were compared by high throughput sequencing of 16S ribosomal DNA (rDNA). Analysis of caecal 16S sequences clearly resolved the mouse lines. The most T1D-susceptible mouse strains had reduced microbiome diversity; about half of sequences from NOD.Tlr1-/- and NOD.Tlr4-/- mice were from Helicobacter and Bacteroides species respectively. Microarray gene expression comparisons of WT NOD, NOD.Tlr1-/- and NOD.Tlr2-/- mice identified highly significant differential expression in multiple pathways affecting the differentiation and integrity of the intestinal mucosa.