A Zebrafish Model of Mycobacterium leprae Granulomatous Infection

Summary The study of leprosy is hampered by the paucity of animal models. This study describes the development of the genetically tractable zebrafish to study leprosy pathogenesis, particularly granuloma formation and function. Abstract Understanding the pathogenesis of leprosy granulomas has been hindered by a paucity of tractable experimental animal models. Mycobacterium leprae , which causes leprosy, grows optimally at approximately 30°C, so we sought to model granulomatous disease in the ectothermic zebrafish. We found that noncaseating granulomas develop rapidly and eventually eradicate infection. rag1 mutant zebrafish, which lack lymphocytes, also form noncaseating granulomas with similar kinetics, but these control infection more slowly. Our findings establish the zebrafish as a facile, genetically tractable model for leprosy and reveal the interplay between innate and adaptive immune determinants mediating leprosy granuloma formation and function.