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

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.

Characterizing the Natural History of Acute Radiation Syndrome of the Gastrointestinal Tract: Combining High Mass and Spatial Resolution Using MALDI-FTICR-MSI

“…MALDI-MSI is an emerging molecular imaging technique that identifies histological regions and cellular content based on label-free detection of their biomolecular profiles. The ability to spatially localize lipids, metabolites, proteins, glycans, drugs and their active metabolites, in serial sections from resected organs and biopsies is putting MSI at the forefront of preclinical, clinical and drug development research (Carter et al 2011;Palmer et al 2012;Steven and Bunch 2013;Powers et al 2015;Harvey et al 2016;Carter et al 2017;Drake et al 2017;Hulme et al 2017;Le Rhun et al 2017;Lukowski et al 2017;Nilsson et al 2017). The application of high-resolution MSI to sections of the jejunum taken from control animals and at days 4, 8, 11, 15 and 21 postexposure enabled the characterization of structural and functional lipids involved in physiological and pathological processes.…”

Dynamic Range Expansion by Gas-Phase Ion Fractionation and Enrichment for Imaging Mass Spectrometry

“…Lipids were identified by searching high resolution accurate mass measurements (HRAM) against the LIPID MAPS (Lipidomics Gateway, www.lipidmaps.org) online database and are reported using total carbon : double bond (TC:DB) sum composition nomenclature. Data analysis was performed using DataAnalysis and Compass IsotopePattern (Bruker Daltonics) as well as the mMass software package.56RESULTSSelective Ion AccumulationContinuous accumulation of selected ions (CASI) has been used by us and others to improve the limit of detection in a variety of IMS applications [44][45][46][47][48][49][50][51]. We seek here to analytically characterize the level of sensitivity and dynamic range improvements that can be achieved by CASI IMS.…”

Quantitative Proteomics and Metabolomics Reveal Biomarkers of Disease as Potential Immunotherapy Targets and Indicators of Therapeutic Efficacy

“…Salmonella , a gram-negative facultative anaerobe, causes almost one billion cases worldwide of foodborne illness per year 96,97. Researchers have recently applied MALDI-MSI to a Salmonella Typhimurium murine model of infection and discovered molecules differentially expressed during infection, one of which was palmitoylcarnitine (PalC) 98. PalC accumulated at the loci of S. Typhimurium infection and resulted in the disruption of mesenteric lymph nodes (MLNs), as shown by the absence of B and T lymphocytes and the altering of subcapsular sinus macrophages.…”