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World J Gastroenterol. Dec 28, 2015; 21(48): 13411-13417
Published online Dec 28, 2015. doi: 10.3748/wjg.v21.i48.13411
On deaf ears, Mycobacterium avium paratuberculosis in pathogenesis Crohn’s and other diseases
William C Davis
William C Davis, Department Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, United States
Author contributions: Davis WC conceived and wrote this manuscript.
Supported by Some of the studies cited here were funded in part with funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. N01-AI-30055, the JDIP program USDA-CSREES-NRI-CAP Award No. 2007-01019 awarded to Davis WC, USDA-NRI grant No. 2005-35204-16106 and the Washington State University Monoclonal Antibody Center.
Conflict-of-interest statement: The author declares no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: William C Davis, PhD, Professor, Department Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, United States. davisw@vetmed.wsu.edu
Telephone: +1-509-3356051 Fax: +1-509-3358328
Received: August 10, 2015
Peer-review started: August 11, 2015
First decision: October 14, 2015
Revised: October 22, 2015
Accepted: November 19, 2015
Article in press: November 19, 2015
Published online: December 28, 2015
Abstract

The historic suggestion that Mycobacterium avium subsp. paratuberculosis (Map) might be a zoonotic pathogen was based on the apparent similarity of lesions in the intestine of patients with Crohn’s disease (CD) with those present in cattle infected with Map, the etiological agent of Johne’s disease. Reluctance to fully explore this possibility has been attributed to the difficulty in demonstrating the presence of Map in tissues from patients with CD. Advances in technology have resolved this problem and revealed the presence of Map in a significant proportion of patients with CD and other diseases. The seminal finding from recent investigations, however, is the detection of Map in healthy individuals with no clinical signs of disease. The latter observation indicates all humans are susceptible to infection with Map and lends support to the thesis that Map is zoonotic, with a latent stage of infection similar to tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of CD and other diseases. As discussed in the present review, a better understanding of the immune response to Map is needed to determine how infection is usually kept under immune control during the latent stage of infection and elucidate the triggering events that lead to disease progression in the natural host and pathogenesis of CD and immune related diseases in humans.

Keywords: Crohn’s disease, Johne’s disease, Mycobacterium avium subsp. paratuberculosis, Animal model, Monoclonal antibodies, Flow cytometry, Cytokines

Core tip: The seminal finding from recent investigations is the detection of Mycobacterium avium subsp. paratuberculosis (Map) in healthy individuals with no clinical signs of disease. The latter observation indicates all humans are susceptible to infection with Mycobacterium avium subsp. paratuberculosis (Map) and lends support to the thesis that Map is zoonotic, with a latent stage of infection similar to M. tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of Crohn’s disease and other diseases.