Veterinary Immunology and Immunopathology 148 (2012) 55–68 Contents lists available at SciVerse ScienceDirect Veterinary Immunology and Immunopathology j ourna l ho me pag e: www.elsevier.com/locate/vetimm Research paper Molecular pathogenesis of bovine paratuberculosis and human inflammatory bowel diseases Eiichi Momotani a,∗ , Ndanyi M. Romona a,1 , Kazuhiro Yoshihara a , Yuriko Momotani a , Masatoshi Hori b , Hiroshi Ozaki b , Shigetoshi Eda c , Masahiro Ikegami d a Research Team for Paratuberculosis, National Institute of Animal Health, 3-1-5 Kan-nondai, Tsukuba 305-0856, Japan b Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan c Center for Wildlife Health, Department of Forestry, Wildlife and Fisheries, The University of Tennessee, Knoxville, TN 37996-1071, USA d Department of Pathology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan a r t i c l e i n f o Keywords: Paratuberculosis Johne’s disease Crohn’s disease Ulcerative colitis IBD Mycobacterium IS900 Immunohistochemistry Pathology Cattle Human PCR a b s t r a c t Paratuberculosis (Ptb), caused by Mycobacterium avium subsp. paratuberculosis (Map), is a chronic enteritis that affects many ruminants and other wild animals worldwide. Ptb is a great concern in animal health and in etiology of human Crohn’s disease (CD). In the present study, we detected Map-specific insertion sequence IS900 of DNA in tissue sec- tions surgically removed from lesions of patients with CD (29 samples), ulcerative colitis (UC) (17 samples), and non-inflammatory bowel disease (IBD) (20 samples). We then com- pared the histopathological findings of 29 CD and 17 UC cases with those of 35 cases of bovine Ptb, since few comparative pathological studies of human IBD and Ptb have been conducted. The QPCR examination indicated positive results in 13.37% of CD cases, 3.57% of UC cases, and 10% of non-IBD cases. Human CD tissues typically exhibited destructive full thickness enteritis with severe lympho-plasma infiltration and scattered additional gran- ulomas; UC lesions exhibited much less inflammation than CD lesions. Non-IBD control samples did not exhibit pathological changes. Human CD and UC lesions were very different from Ptb lesions that are characterized by predominant granuloma formation. Immunohis- tochemistry for Map antigen and acid-fast staining were negative in all human IBD cases but were always positive in Ptb cases. Our present comparative study strongly suggests that we reconsider the previous hypothesis that “Map infection” causes CD, even though human intestines were considered to have been exposed to the Map antigen containing the DNA. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Paratuberculosis (Ptb), caused by Mycobacterium avium subsp. paratuberculosis (Map), is a chronic granuloma- tous enteritis that affects domestic and wild ruminants and other animals worldwide (Nielsen and Toft, 2009; ∗ Corresponding author. Tel.: +81 29 838 7781; fax: +81 29 838 7781. E-mail address: eiichi@momotani.com (E. Momotani). 1 Current address: Central Veterinary Investigation Laboratories, P.O. Box Private Bag Kabete, 00625 Kangemi, Nairobi, Kenya. Stabel et al., 2009). Prevalence of this infection in cattle in Australia, New Zealand, Europe, and the USA ranges from 10 to 60% (Harris and Barletta, 2001). In Japan, 1000 of every officially examined 500,000 cattle annually are diag- nosed as having Ptb (the Japanese Animal Health Statistics; MAFF, 2009). Ptb is thus the greatest economical problem in animal health (Raizman et al., 2009; Stabel, 1998). The first report of isolation of Map in several Crohn’s disease (CD) patients appeared in 1984 (Chiodini et al., 1984b,c). Since then, much suggestive evidence has been accumu- lated, and interest in the importance of Map in food safety has increased (Chiodini, 1989; Chiodini and Rossiter, 1996; 0165-2427/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2012.03.005