A University of Washington study is the first to provide visualizations of TB infections in an intact living organism and to reveal how TB granulomas -- tight aggregates of macrophages that indicate the infection -- are formed within infected organisms. Dr. Lalita Ramakrishnan, UW assistant professor of microbiology and medicine, and colleagues used direct imaging of labeled bacteria in developing zebrafish embryos to examine how TB bacteria exploit the behavior of macrophages to evade the body's immune system, multiply and, through a still-unknown signaling pathway, cause the infected macrophages to gather into granulomas. Granulomas can form in any part of the human body; researchers have long suspected that they serve as a reservoir for recurring bouts of TB infection.

"This is the first time that an infection has been followed visually in an intact organism like this," Ramakrishnan said. "Zebrafish have become a favorite organism of developmental biologists because they are optically transparent, allowing researchers to visualize processes in living animals."

Ramakrishnan and colleagues filmed the dynamics of infected macrophages within living granulomas. They used Mycobacterium marinum, a close relative of TB bacteria and a natural pathogen of zebrafish, and discovered at least two separate routes by which TB bacteria can move from infected to uninfected macrophages. A dying macrophage that contains TB bacteria can be engulfed by an uninfected macrophage, or direct transfer of TB bacteria can occur between macrophages via intercellular protrusions.

The study, "Real-Time Visualization of Mycobacterium-Macrophage Interactions Leading to Initiation of Granuloma Formation in Zebrafish Embryos," was published in Immunity (2002;17(6):693-702).

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