Tuberculosis Granulomas May Aid Infecting Bacteria

Formation of granulomas in the lungs of tuberculosis sufferers may be due to deliberate bacterial activity rather than as a host protective response, which has been the common belief.

Investigators at the University of Washington (Seattle, USA) working with a model system comprising zebrafish infected with Mycobacterium marinum used quantitative intravital microscopy to reveal distinct steps of granuloma formation and assess their consequence for infection.

They reported in the January 9, 2009, issue of the journal Cell that intracellular mycobacteria used the ESX-1/RD1 virulence locus to induce recruitment of new macrophages to, and their rapid movement within, emerging granulomas. This motility enabled multiple arriving macrophages to efficiently find and engulf infected macrophages undergoing apoptosis. This led to the rapid, repetitive expansion of infected macrophages, and in turn, bacterial numbers. The primary granuloma then seeded secondary granulomas through the exit of infected macrophages.

"The bacteria in all the exiting macrophages remained fully viable after departure and had the potential to initiate new granulomas,” said senior author Dr. Lalita Ramakrishnan, associate professor of microbiology, medicine, and immunology at the University of Washington. "The macrophages exiting the original granuloma were leaving to seed distant granulomas to spread the infection. Tubercles or granulomas have long been considered host-protective. What we observed completely overturns the fundamental dogma on their role, at least early in infection.”

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