Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

HULME, H. E. et al. (2017) Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection. Scientific Reports, 7, 2786. (doi: 10.1038/s41598-017-03100-5) (PMID:28584281) (PMCID:PMC5459799)

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Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Thomson, Miss Carolyn and Wall, Dr Daniel and Milling, Professor Simon and HULME, Heather and Goodwin, Dr Richard and Burchmore, Dr Richard and Nibbs, Professor Rob and Meikle, Dr Lynsey and Wessel, Miss Hannah
Authors: HULME, H. E., Meikle, L. M., Wessel, H., Strittmatter, N., Swales, J., Thomson, C., Nilsson, A., Nibbs, R. J.B., Milling, S., Andren, P. E., Mackay, C. L., Dexter, A., Bunch, J., Goodwin, R. J.A., Burchmore, R., and Wall, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7: 2786
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607841Survival and dissemination of enteric pathogens through exploitation and inhibition of programmed cell death pathways in circulating immune cells.Daniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/K008005/1III - BACTERIOLOGY