Macrophage activation, measured as increased acid phosphatase (AcPase)-positive areas by image analysis, and ultrastructural features were examined in granulomatous mycobacterial lesions of mice innately susceptible (BALB/c mice; Bcg) and innately resistant (C3H/HeJ mice; Bcg) to Mycobacterium paratuberculosis strain ATCC 19698. In the liver and spleen of BALB/c mice 3 weeks after intraperitoneal inoculation with M. paratuberculosis, AcPase activity detected in epithelioid cell nodules was high; it had decreased, however, in the liver and spleen after a further 3 and 6 weeks, respectively. In C3H/HeJ mice, the size of epithelioid cell nodules in the liver and spleen was smaller than in BALB/c mice, and infiltrating macrophages, which had increased by week 9 after inoculation, showed high AcPase activity. Ultrastructurally, by week 32 in BALB/c mice, small phagolysosomes (SPLs) had greatly increased in number in the epithelioid cell. These SPLs contained a few AcPase-positive areas and a small number of bacteria, most of which were surrounded by an electron-translucent space (or electron-transparent zone [ETZ]). In contrast, only a few SPLs were observed in C3H/HeJ mice at week 32; in the liver and spleen, large phagolysosomes (LPLs) showed high AcPase activity and contained many degenerated bacteria, which also had an ETZ. These results suggest that the enzymatic and ultrastructural differences in phagolysosomes between BALB/c mice and C3H/HeJ mice reflect the susceptibility of these mouse strains to M. paratuberculosis.
