A Zebrafish Model For Mycobacterium leprae Granulomatous Infection

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 ~30{degrees}C, so we sought to model granulomatous disease in the ectothermic zebrafish. We find 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.