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...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.展开更多
基金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-30055the JDIP program USDA-CSREES-NRI-CAP Award No.2007-01019 awarded to Davis WC+1 种基金USDA-NRI grant No.2005-35204-16106the Washington State University Monoclonal Antibody Center
文摘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.
