Adult zebrafish are susceptible to Mycobacterium leprae infection. A, Hematoxylin-eosin (H-E)–stained section of a granuloma in the peritoneal cavity of a wild-type adult zebrafish 7 days after infection with 5 × 10⁷ Thai53 strain M. leprae. Arrowheads indicate lymphocyte nuclei. B, Granuloma from a skin biopsy specimen from a patient with tuberculoid leprosy. The image is from the archives of the Lauro de Souza Lima Institute. C, Serial section of the granuloma in panel A, stained for acid-fast bacilli (AFB) to detect M. leprae; many bacteria are present (arrows). D, AFB-stained granuloma section from the peritoneal cavity of a similarly infected fish, 7 days after infection; few bacteria are present. Arrows indicate bacilli. Bars denote 10 μm.

Adaptive immunity contributes to control of Mycobacterium leprae infection. A, Representative images of sibling uninfected and infected rag1 mutant animals approximately 100 days after infection; the M. leprae–infected animal is smaller than the uninfected animal. Arrows indicate an intact fin in the uninfected animal and a frayed fin in the infected animal. B, Kaplan-Meier survival curve of sibling rag1 heterozygote and mutant zebrafish with or without infection due to M. leprae as described in Figure 1A. There were 61 uninfected heterozygotes, 20 infected heterozygotes, 57 uninfected mutants, and 41 infected mutants. C, Hematoxylin-eosin (H-E)–stained section of a rag1 mutant zebrafish granuloma, infected as described in Figure 1A. Bar denotes 10 μm. D, Quantification of bacterial burden per fish in rag1 heterozygotes and mutants. *P = .03, by the Student t test, comparing heterozygotes to mutants at each time point. Other comparisons were not significant.

Detailed analysis of M. leprae granulomas. In panel A, multiple AFB-stained sections from infected fish at 112 dpi were scored for number of infected granulomas; n, number of sections scored. In panel B, an AFB-stained section of a non-necrotizing granuloma in a rag1 heterozygote zebrafish with heavily infected macrophages (arrows). In panel C, AFB and H&E sections of a necrotic granuloma observed in M. leprae-infected rag1 heterozygote fish. 10μm bars.