Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection.
Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection.
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DOI：
10.1038/s41598-017-03100-5
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发表时间：
2017-06-05
影响因子：
4.6
通讯作者：
Wall DM
中科院分区：
文献类型：
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作者：
Hulme HE;Meikle LM;Wessel H;Strittmatter N;Swales J;Thomson C;Nilsson A;Nibbs RJB;Milling S;Andren PE;Mackay CL;Dexter A;Bunch J;Goodwin RJA;Burchmore R;Wall DM
鼠伤寒沙门氏菌引起自限性胃肠炎，可能导致全身性疾病。细菌侵入小肠，穿过肠道上皮，从那里运输到迁移免疫细胞内的肠系膜淋巴结(MLN)。MLN是先天免疫和获得性免疫反应融合的重要部位，但其结构和功能在鼠伤寒沙门氏菌感染过程中受到严重破坏。为了进一步了解宿主-病原体在这个部位的相互作用，我们使用质谱仪成像(MSI)分析了鼠伤寒沙门氏菌感染模型的MLN组织。棕榈酰肉碱(Palmitoylcarnitine，Palmtoylcarnitine)由于在鼠伤寒沙门氏菌感染和mln破坏的基因座上具有很高的丰度而引起人们的特别关注。高水平的PalC定位于MLN内B和T细胞缺失以及CD169+被膜下巨噬细胞周长被破坏的部位。体外培养的MLN细胞经PalC处理后，CD4+CD25+T细胞减少，B220+CD19+B细胞增加。CD4+CD25+T细胞的减少可能是由于caspase-3/7活性增加导致的细胞凋亡。这些数据表明，PalC显著改变了MLN中的宿主反应，对感染结果起着决定性的作用。
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.