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Sci Rep. 2017 Jun 5;7(1):2786. doi: 10.1038/s41598-017-03100-5.

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

Author information

1
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
2
AstraZeneca, Milton Science Park, Cambridge, CB4 0WG, United Kingdom.
3
Biomolecular Imaging and Proteomics, Department of Pharmaceutical Biosciences, Uppsala University, Box 591 BMC, Uppsala, 751 24, Sweden.
4
School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, United Kingdom.
5
National Physical Laboratory, Teddington, Middlesex, TW11 0LW, United Kingdom.
6
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. richard.burchmore@glasgow.ac.uk.
7
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. donal.wall@glasgow.ac.uk.

Abstract

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.

PMID:
28584281
PMCID:
PMC5459799
DOI:
10.1038/s41598-017-03100-5
[Indexed for MEDLINE]
Free PMC Article

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