Fish monocytes as a model for mycobacterial host-pathogen interactions

Mycobacterium marinum, a relatively rapid-growing fish and human pathogen, has become an important model for the investigation of mycobacterial pathog enesis. Al. marinum is closely related to the Mycobacterium tuberculosis co mplex and causes a disease in fish and amphibians with pathology similar to tuberculosis. We have developed an in vitro model for the study of M. mari num virulence mechanisms using the carp monocytic cell line CLC (carp leuko cyte culture). We found that fish monocytes can differentiate between patho genic and nonpathogenic mycobacterial species. Interestingly, M. marinum en ters fish monocytes at a 40- to 60-fold-higher rate than Mycobacterium smeg matis. In addition, M. marinum survives and replicates in fish monocytes wh ile M. smegmatis is killed. We also found that M. marinum inhibits lysosoma l fusion in fish monocytes, indicating that these cells may be used to diss ect the mechanisms of intracellular trafficking in mycobacteria. We conclud e from these observations that monocytic cells from fish, a natural host fo r Al. marinum, provide an extremely valuable model for the identification a nd characterization of mycobacterial virulence determinants in the laborato ry.