FIG. 2.

Zebrafish tuberculosis disease progression is characterized by progressive necrosis and pigment deposition with large numbers of bacteria found within necrotic granulomas. Adult zebrafish were infected with 5 CFU of wild-type M. marinum, and histology was assessed at 2 weeks (A and B), 8 weeks (C, D, E, and F), and 16 weeks (G, H, I, and J) postinfection with hematoxylin and eosin (A, C, E, G, and I) and Ziehl-Neelson (B, D, F, H, and J) staining of serial sections. (A and B) Early, loosely associated, nonnecrotic lesions (arrows) with early cellular breakdown in the gonad (teste) composed of an epithelioid macrophage infiltrate surrounding scattered mycobacteria. The inset in B shows a higher-magnification view of acid-fast bacteria residing within macrophages. (C and D) Well-organized, nonnecrotizing granuloma in the liver with clear areas between macrophages reflecting either early necrosis or less interdigitation of the macrophages. (E and F) Necrotizing granuloma in the liver with areas of partial (dashed lines) and complete (arrow) necrosis and acid-fast bacilli (arrowheads) residing predominantly within the necrotic areas. (G and H) Late-stage lesion in the liver with a thin, well-defined macrophage border (arrow) and prominent central necrosis (dashed lines). Note the high bacterial numbers present in the central, necrotic core in H (arrowhead). (I and J) Multicentric necrotic lesions in the head kidney during late-stage disease with extensive pigment deposition (arrowheads). Scale bars, 50 μm. Magnifications, ×200 for A, B, I, and J and ×400 for all other panels.