Fish Monocytes as a Model for Mycobacterial Host-Pathogen Interactions

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Abstract
Mycobacterium marinum, a relatively rapid-growing fish and human pathogen, has become an important model for the investigation of mycobacterial pathogenesis.M. marinumis closely related to theMycobacterium tuberculosiscomplex and causes a disease in fish and amphibians with pathology similar to tuberculosis. We have developed an in vitro model for the study ofM. marinumvirulence mechanisms using the carp monocytic cell line CLC (carp leukocyte culture). We found that fish monocytes can differentiate between pathogenic and nonpathogenic mycobacterial species. Interestingly,M. marinumenters fish monocytes at a 40- to 60-fold-higher rate thanMycobacterium smegmatis. In addition,M. marinumsurvives and replicates in fish monocytes whileM. smegmatisis killed. We also found thatM. marinuminhibits lysosomal fusion in fish monocytes, indicating that these cells may be used to dissect the mechanisms of intracellular trafficking in mycobacteria. We conclude from these observations that monocytic cells from fish, a natural host forM. marinum, provide an extremely valuable model for the identification and characterization of mycobacterial virulence determinants in the laboratory.