Intracellular trafficking of Mycobacterium avium ss. paratuberculosis in macrophages

The granulomatous enteric lesions of cattle with Johne's disease are compos ed of infected macrophages, and grow by accumulation, re-infection, and exp ansion of macrophage populations in the intestinal wall. We have examined t he growth of bacteria in macrophages to define characteristics of intracell ular trafficking for exocytosis, replication, and antigen presentation. Usi ng immunocytochemical markers for light, confocal and electron microscopy, we have examined potential pathway tropisms using data for bacterial attach ment, phagosomal acidification, phagolysosomal degradation and apoptosis. O ur hypotheses are that pathogenic/wild-type strains block phagosomal acidif ication so that the phagosome fails to obtain markers of the late phagosome and phagolysosome, and this leads to the replication pathway within bacter iophorous vacuoles. Non-pathogenic strains appear to be processed to exocyt osis, and avirulent mutant strains may be degraded and have preference of a ntigen processing pathways that involve transport vesicles bearing MHC II a ntigens. Pathogenicity in a nude mouse model of intestinal infection reveal s lesion development and confirms pathway preferences of virulent strains f or bacteriophorous vacuole formation.