Dataset Information

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.

SUBMITTER: Hulme HE

PROVIDER: S-EPMC5459799 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hulme Heather E HE Meikle Lynsey M LM Wessel Hannah H Strittmatter Nicole N Swales John J Thomson Carolyn C Nilsson Anna A Nibbs Robert J B RJB Milling Simon S Andren Per E PE Mackay C Logan CL Dexter Alex A Bunch Josephine J Goodwin Richard J A RJA Burchmore Richard R Wall Daniel M DM

Scientific reports 20170605 1

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 th ...[more]

PMID: 28584281

Similar Datasets

Project description:IntroductionSpatial analysis of lipids in inflammatory microenvironments is key to understand the pathogenesis of infectious disease. Granulomatous inflammation is a hallmark of leishmaniasis and changes in host and parasite lipid metabolism have been observed at the bulk tissue level in various infection models. Here, mass spectrometry imaging (MSI) is applied to spatially map hepatic lipid composition following infection with Leishmania donovani, an experimental mouse model of visceral leishmaniasis.MethodsLivers from naïve and L. donovani-infected C57BL/6 mice were harvested at 14- and 20-days post-infection (n=5 per time point). 12 µm transverse sections were cut and covered with norhamane, prior to lipid analysis using MALDI-MSI. MALDI-MSI was performed in negative mode on a Rapiflex (Bruker Daltonics) at 5 and 50 µm spatial resolution and data-dependent analysis (DDA) on an Orbitrap-Elite (Thermo-Scientific) at 50 µm spatial resolution for structural identification analysis of lipids.ResultsAberrant lipid abundances were observed in a heterogeneous distribution across infected mouse livers compared to naïve mouse liver. Distinctive localized correlated lipid masses were found in granulomas and surrounding parenchymal tissue. Structural identification revealed 40 different lipids common to naïve and d14/d20 infected mouse livers, whereas 15 identified lipids were only detected in infected mouse livers. For pathology-guided MSI imaging, we deduced lipids from manually annotated granulomatous and parenchyma regions of interests (ROIs), identifying 34 lipids that showed significantly different intensities between parenchyma and granulomas across all infected livers.DiscussionOur results identify specific lipids that spatially correlate to the major histopathological feature of Leishmania donovani infection in the liver, viz. hepatic granulomas. In addition, we identified a three-fold increase in the number of unique phosphatidylglycerols (PGs) in infected liver tissue and provide direct evidence that arachidonic acid-containing phospholipids are localized with hepatic granulomas. These phospholipids may serve as important precursors for downstream oxylipin generation with consequences for the regulation of the inflammatory cascade. This study provides the first description of the use of MSI to define spatial-temporal lipid changes at local sites of infection induced by Leishmania donovani in mice.

Project description:Members of Salmonella enterica are frequently involved in egg and egg product related human food poisoning outbreaks worldwide. In Australia, Salmonella Typhimurium is frequently involved in egg and egg product related foodborne illness and Salmonella Mbandaka has also been found to be a contaminant of the layer farm environment. The ability possessed by Salmonella Enteritidis to colonize reproductive organs and contaminate developing eggs has been well-described. However, there are few studies investigating this ability for Salmonella Typhimurium. The hypothesis of this study was that the Salmonella Typhimurium can colonize the gut for a prolonged period of time and that horizontal infection through feces is the main route of egg contamination. At 14 weeks of age hens were orally infected with either S. Typhimurium PT 9 or S. Typhimurium PT 9 and Salmonella Mbandaka. Salmonella shedding in feces and eggs was monitored for 15 weeks post-infection. Egg shell surface and internal contents of eggs laid by infected hens were cultured independently for detection of Salmonella spp. The mean Salmonella load in feces ranged from 1.54 to 63.35 and 0.31 to 98.38 most probable number/g (MPN/g) in the S. Typhimurium and S. Typhimurium + S. Mbandaka group, respectively. No correlation was found between mean fecal Salmonella load and frequency of egg shell contamination. Egg shell contamination was higher in S. Typhimurium + S. Mbandaka infected group (7.2% S. Typhimurium, 14.1% S. Mbandaka) compared to birds infected with S. Typhimurium (5.66%) however, co-infection had no significant impact on egg contamination by S. Typhimurium. Throughout the study Salmonella was not recovered from internal contents of eggs laid by hens. Salmonella was isolated from different segments of oviduct of hens from both the groups, however pathology was not observed on microscopic examination. This study investigated Salmonella shedding for up to 15 weeks p.i which is a longer period of time compared to previously published studies. The findings of current study demonstrated intermittent but persistent fecal shedding of Salmonella after oral infection for up to 15 weeks p.i. Further, egg shell contamination, with lack of internal egg content contamination and the low frequency of reproductive organ infection suggested that horizontal infection through contaminated feces is the main route of egg contamination with S. Typhimurium in laying hens.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets