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Pathogenesis of Tuberculosis

Zebrafish as model to study immunity to tuberculosis

tb imageThe research led by Professor Ramakrishnan is interested in understanding the pathogenesis of tuberculosis and the basis of vastly different susceptibilities to this disease. Tuberculous infection results in the formation of granulomas, complex immune structures that are composed of differentiated macrophages, lymphocytes and otherimmune cells. However, bacteria can persist within granulomas despite the development of antigen-specific immunity.

To understand the mechanistic basis of mycobacterial persistence, the mechanisms of granuloma formation and its role in tuberculosis, they have  developed the zebrafish as model to study immunity to tuberculosis.

Zebrafish are naturally susceptible to tuberculosis caused by Mycobacterium marinum, a close genetic relative of M. tuberculosis, the agent of human tuberculosis. Their research is shedding light on TB pathogenesis as well as fundamental mechanisms of immune cell chemotaxis, adhesion and aggregation as well as immune regulation. 

 

Publications

iBiology talk on Tuberculosis Pathogenesis - https://www.ibiology.org/human-disease/tuberculosis-pathogenesis/

C.J. Cambier, S.M. O'Leary, M.P. O'Sullivan, J. Keane, L. Ramakrishnan 2017.  Phenolic Glycolipid facilitates mycobacterial escape from microbicidal tissue-resident macrophages. Immunity 47:552-565 https://doi.org/10.1016/j.immuni.2017.08.003

C. A. Madigan, J. Cameron, L. Ramakrishnan. 2017. A zebrafish model of Mycobacterium leprae granulomatous infection. J Infect Dis 16:776-779  https://doi.org/10.1093/infdis/jix329

C.A. Madigan, C.J. Cambier, K.M. Kelly-Scumpia, P.O. Scumpia, T.Y. Cheng, J. Zailaa, B.R. Bloom, D.B. Moody, S.T. Smale, A. Sagasti, R.L. Modlin, L. Ramakrishnan. 2017. A macrophage response to Mycobacterium leprae phenolic glycolipid initiates nerve damage in leprosy. Cell:170:973-985.  https://doi.org/10.1016/j.cell.2017.07.030

 

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Even without lungs, zebrafish help us study TB

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The Centre supports collaborative partnerships and scientific training activities in basic biomedical and health-related research. This is achieved through coordinated cross-faculty research across departments and research institutes in Cambridge including The Wellcome Trust Sanger Institute