Looking Within the Zebrafish to Understand the Tuberculous Granuloma

  • Lalita Ramakrishnan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 783)


Tuberculosis is characterized by the formation of complex immune cell aggregates called granulomas, which for nearly a century have been viewed as critical host-beneficial structures to restrict bacterial growth and spread. A different view has now emerged from real-time visualization of granuloma formation and its consequences in the optically transparent and genetically tractable zebrafish larva. Pathogenic mycobacteria have developed mechanisms to use host granulomas for their expansion and dissemination, at least during the innate phases of infection. Host processes that are intended to be beneficial—death of infected macrophages and their subsequent phagocytosis by macrophages that are newly recruited to the growing granuloma—are harnessed by mycobacteria for their own benefit. Mycobacteria can also render the granuloma a safe-haven in the more advanced stages of infection. An understanding of the host and bacterial pathways involved in tuberculous granuloma formation may suggest new ways to combat mycobacterial infection.


Tubercles Tuburculous granuloma Mycobacterium tuberculosis Macrophages Necrosis Mycobacterium marinum Zebrafish Tumor necrosis factor Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine strain Neutrophils Cell death Host matrix metalloproteinase 9 (MMP9) Apoptosis Mycobacteria 



The research presented in this chapter has been supported by grants from the National Institutes of Health, including the NIH Director’s Pioneer Award, as well as the Burroughs Wellcome Award in the Pathogenesis of Infectious Diseases, the Ellison Medical Foundation, the Keck Foundation, and the Akibene Foundation. I thank Christine Cosma for discussion and critical review of the manuscript and Tiffany Pecor for help with manuscript preparation.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Microbiology, Medicine and ImmunologyUniversity of WashingtonSeattleUSA

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