Role of complement receptors in uptake of Mycobacterium avium by macrophages in vivo: evidence from studies using CD18-deficient mice

Abstract

Mycobacterium avium is an intracellular pathogen that has been shown to invade macrophages by using complement receptors in vitro, but mycobacteria released from one cell can enter a second macrophage by using receptors different from complement receptors. Infection of CD18 (beta(2) integrin) knockout mice and the C57 BL/6 control mice led to comparable levels of tissue infection at 1 day, 2 days, 1 week, and 3 weeks following administration of bacteria. A histopathological study revealed similar granulomatous lesions in the two mouse strains, with comparable numbers of organisms. In addition, transmission electron microscopy of spleen tissues from both strains of mice showed bacteria inside macrophages. Our in vivo findings support the hypothesis that M. avium in the host is likely to use receptors other than CR3 and CR4 receptors to enter macrophages with increased efficiency.

FIG. 1

Histopathology of mouse spleens, stained for acid-fast bacilli, from CD18 KO mice (panels 1 and 3) and C57 BL/6 (panels 2 and 4). Granulomatous lesions containing mycobacteria and epithelioid cells can be observed. Spleens were obtained 1 week (panels 1 and 2) and 3 weeks (panels 3 and 4) after infection.

FIG. 2

Electron micrographs of the spleens of CD18 KO mice (panels 1 and 3) and C57 BL/6 mice (panels 2 and 4). Panels 1 and 2 were obtained at 1 week postinfection; panels 3 and 4 were obtained at 3 weeks postinfection. Bacteria are seen within macrophage vacuoles in all examples.