The secret world of inflammation is slowly being revealed by the application of advanced techniques in microscopy, as shown in a study published March 12 in the open-access journal PLoS Pathogens. Researchers at the Hull York Medical School and the University of York used 2-photon microscopy to identify how killer T lymphocytes behaved when they enter sites of inflammation caused by the parasite Leishmania donovani, and which infected cells they were able to recognise.
Leishmaniasis is a globally important but neglected disease, affecting approximately two million people every year. For most people, infection results in a slow-to-heal skin ulcer. In others, however, the parasite targets the liver, spleen and bone marrow, leading to over 70,000 deaths annually.
The Leishmania parasite is eventually contained by a characteristic type of inflammatory response that forms cellular structures called 'granulomas'. Little is known about the inner workings of these granulomas, in spite of their occurrence in other human diseases, from tuberculosis to rheumatoid arthritis.
The York-based research team used an advanced laser-based microscopy technique, called '2-photon imaging', to view the inner workings of the granuloma in mice infected with Leishmania. This enabled them to study how killer lymphocytes, such as those that can be induced by vaccination, are able to enter into the granulomas, penetrate deep into the core of the structure and seek out specific types of parasite-infected cells.
Although this technique can not be used currently for the study of inflammatory disease in humans, the insights provided into the biology of granulomas and the hidden world of inflammation should help to improve vaccines and drugs, and allow researchers to now construct in silico models for this type of inflammatory process.
FINANCIAL DISCLOSURE: This work was supported by the Wellcome Trust (#077503 to DFS; #084534 to PMK and AK) and the U.K. Medical Research Council (G0400786 to PMK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1000805 (link will go live upon embargo lift)
CITATION: Beattie L, Peltan A, Maroof A, Kirby A, Brown N, et al. (2010) Dynamic Imaging of Experimental Leishmania donovani-Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8+ T Cells. PLoS Pathog 6(3): e1000805. doi:10.1371/journal.ppat.1000805
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