4th Annual BMRP Investigator Meeting - Abstract
Mycobacterium avian ss paratuberculosis Promotes but Does Not Cause Crohn’s Disease
Robert Clancy1,2,a, Zhigang Ren1, Jacqueline Turton1, Tom Borody3 and Gerald Pang1
1School of Biomedical Sciences, University of Newcastle, (Callaghan, New South Wales, Australia); 2 Hunter Immunology Unit, Hunter Area Pathology Service, Hunter New England Area Health Service, John Hunter Hospital (New Lambton, New South Wales, Australia); 3Centre for Digestive Diseases (Five Dock, New South Wales, Australia)
The concept that Crohn’s disease (CD) is caused/promoted by infection with Mycobacterium avian ss paratuberculosis (MAP) is supported only by controversial epidemiological data. The aim of this study was to determine whether there was any correlation between MAP infection and the pattern of secreted cytokines from gut mucosal organ cultures. 228 subjects were recruited: 61 with CD, 49 with ulcerative colitis, 45 with irritable bowel syndrome and 73 normals. MAP status was defined by nested PCR using the IS900 sequence. Two significant differences were observed: (i) an increase in TNFα secretion was detected in MAP +ve subjects, but only in CD (p=0.03) and (ii) IL-2 and IL-4 (but not INF-γ) secretion in MAP +ve subjects was increased in whole blood cultures, again selectively in CD (p=0.011 and 0.004, respectively). We conclude that CD is characterized by defective macrophage function with abnormal handling of MAP resulting in inappropriate TNFα secretion. Circulating macrophages containing MAP stimulate primed CD4+ve T cells to secrete Th2 cytokines. This is the first data linking MAP infection in CD to a pathogenic mechanism(s).
aPrincipal Investigator