Mycobacterium avium subsp. paratuberculosis lipophilic antigen causes Crohn’s disease-type necrotizing colitis in Mice

Abstract

Background: A 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model was developed to investigate the pathogenesis and to evaluate a method of treating human Crohn’s disease. This experimental model rapidly induces colitis similar to human Crohn’s disease lesion in a reproducible manner. However, natural exposure of the human digestive tract to TNBS is unrealistic. A novel animal model based on realistic data is eagerly anticipated in future research on pathogenesis of CD. Method: We evaluated the potency of Map antigen molecules in an effort to develop a novel colitis model using a more realistic source than TNBS. We prepared the Map antigen by ethanol extraction and developed a mouse model in a manner similar to that of the well-known TNBS-induced colitis in mice. In the experiment, seven days after subcutaneous (SC) injection of the antigen into normal C57BL/6 mice, the same antigen in 50% ethanol was injected into the colon by the transanal route with a fine cannula. Results: On the fifth day after the transanal injection, histopathological examination revealed full-thickness necrotizing colitis with erosion and ulcers; severe infiltration with neutrophils, lymphocytes, macrophages, and perforation. However, no change was detected with each single Map-antigen injection. Conclusion: The present results provide a novel animal model for research on CD and may be the key to clarifying the relationship between CD and Map. This is the first evidence that mycobacterium antigen induces necrotizing colitis.

Detection of Mycobacteria by Culture and DNA-Based Methods in Animal-Derived Food Products Purchased at Spanish Supermarkets

“…avium subsp. paratuberculosis antigens (Momotani et al, 2012 ). However, our results do not indicate that a heavy foodborne exposure occurs in populations where the main source of food of animal origin is processed food.…”

Mycobacterium aviumsubspeciesparatuberculosis –an important food borne pathogen of high public health significance with special reference to India: an update

“…However, the causal association of MAP with CD remains controversial (Miller et al 1996). Momotani et al (2012) proposed a novel mouse model for CD-like colitis and the ability of MAP antigen to induce necrotizing colitis, which may be the key to understanding the relationship between CD and MAP. This model may help clarify the pathogenesis of CD, as well as other diseases with a suspected etiological relationship to MAP, e.g.…”

Mycobacteria in water, soil, plants and air: a review

“…N-glycolyl MDP is produced by degradation of mycobacterial peptidoglycans. The importance of a lipid antigen in the molecular pathogenesis of ruminant paratuberculosis and human inflammatory bowel diseases are subjects of recently published data (Momotani et al 2012;Mori and De Libero 2012). It is evident that under specific conditions mycobacteria can be zoonotic or environmental pathogens for humans and an agents that participate in foodborne autoimmune or autoinflammatory human diseases.…”