Nov. 5, 2004 Fighting an infection might seem to be a battle between David and Goliath, given the relative sizes of bacterial infectious agents and the animals they infect. But on closer examination it is more often a chess match between two skilled opponents who have the uncanny ability to anticipate each other's moves. An example is provided by the interaction between Mycobacterium tuberculosis, which causes tuberculosis (TB), and its human host. One of the host's first moves against the mycobacterium is the formation of a granuloma, an aggregate of cells, which consists of macrophages and other defensive immune cells. Although granulomas are required for the elimination of the infection, Lalita Ramakrishnan and colleagues have now shown that the bacteria have a game plan of their own.
One problem in understanding the interaction between the mycobacterium and the host has been that it occurs deep in the lung of the infected animal. To overcome this limitation, Ramakrishnan and colleagues used zebrafish embryos, which are transparent and can be infected by a relative of the TB pathogen, M. marinum. This enables the researchers to watch cells as they are recruited into the granuloma.
By visualizing in zebrafish infections of a virulent strain of M. marinum and a strain missing a genetic region called RD1 – a region that is somehow involved in the virulence of the bacteria – Ramakrishnan and colleagues have observed that RD1 is actually required for granuloma formation and even recruits more macrophages to granulomas. This might seem an odd strategy, as macrophages are required for mycobacterial elimination. But in this ongoing chess match, the virulent mycobacterium exploits the host's defense--granuloma formation--by providing additional macrophages for the bacteria to infect.
The end game of the chess match remains unclear. While granulomas are required for protection against mycobacteria, they are not completely effective. Thus, these bacteria have developed a strategy to recruit the normally defensive cells of the host to their advantage, but it remains to be shown what tips the balance between the macrophages' ability to clear the infection and their unwitting participation in the development of TB.
Citation: Volkman HE, Clay H, Beery D, Change JCW, Sherman DR, et al (2004) Tuberculous granuloma formation is enhanced by a Mycobacterium virulence determinant. PLoS Biol 2 (11): e367.
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