Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada.
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
Front Immunol. 2021 Dec 15;12:760931. doi: 10.3389/fimmu.2021.760931. eCollection 2021.
subsp. (MAP) is the causative infectious agent of Johne's disease (JD), an incurable granulomatous enteritis affecting domestic livestock and other ruminants around the world. Chronic MAP infections usually begin in calves with MAP uptake by Peyer's patches (PP) located in the jejunum (JE) and ileum (IL). Determining host responses at these intestinal sites can provide a more complete understanding of how MAP manipulates the local microenvironment to support its long-term survival. We selected naturally infected (MAPinf, n=4) and naive (MAPneg, n=3) cows and transcriptionally profiled the JE and IL regions of the small intestine and draining mesenteric lymph nodes (LN). Differentially expressed (DE) genes associated with MAP infection were identified in the IL (585), JE (218), jejunum lymph node (JELN) (205), and ileum lymph node (ILLN) (117). Three DE genes (, and ) were common to all MAPinf MAPneg tissues. Functional enrichment analysis revealed immune/disease related biological processes gene ontology (GO) terms and pathways predominated in IL tissue, indicative of an activated immune response state. Enriched GO terms and pathways in JE revealed a distinct set of host responses from those detected in IL. Regional differences were also identified between the mesenteric LNs draining each intestinal site. More down-regulated genes (52%) and fewer immune/disease pathways (n=5) were found in the ILLN compared to a higher number of up-regulated DE genes (56%) and enriched immune/disease pathways (n=13) in the JELN. Immunohistochemical staining validated myeloid cell transcriptional changes with increased CD172-positive myeloid cells in IL and JE tissues and draining LNs of MAPinf MAPneg cows. Several genes, GO terms, and pathways related to metabolism were significantly DE in IL and JE, but to a lesser extent (comparatively fewer enriched metabolic GO terms and pathways) in JELN suggesting distinct regional metabolic changes in IL compared to JE and JELN in response to MAP infection. These unique tissue- and regional-specific differences provides novel insight into the dichotomy in host responses to MAP infection that occur throughout the small intestine and mesenteric LN of chronically MAP infected cows.
（MAP）亚种是约翰氏病（JD）的致病感染因子，JD 是一种影响全球家畜和其他反刍动物的无法治愈的肉芽肿性肠炎。慢性 MAP 感染通常始于幼牛，幼牛通过位于空肠（JE）和回肠（IL）的派尔集合淋巴结（PP）摄取 MAP。确定这些肠道部位的宿主反应可以更全面地了解 MAP 如何操纵局部微环境以支持其长期存活。我们选择了自然感染（MAPinf，n=4）和未感染（MAPneg，n=3）的奶牛，并对小肠的 JE 和 IL 区域以及引流肠系膜淋巴结（LN）进行了转录谱分析。在 IL（585）、JE（218）、空肠淋巴结（JELN）（205）和回肠淋巴结（ILLN）（117）中鉴定出与 MAP 感染相关的差异表达（DE）基因。三个 DE 基因（、和）在所有 MAPinf 和 MAPneg 组织中都是共同的。功能富集分析显示，免疫/疾病相关的生物学过程基因本体（GO）术语和途径在 IL 组织中占主导地位，表明存在激活的免疫反应状态。在 JE 中发现的富集 GO 术语和途径与在 IL 中检测到的截然不同。从每个肠道部位引流的肠系膜 LN 之间也存在区域差异。与 JELN 相比，ILLN 中下调的基因（52%）更多，免疫/疾病途径（n=5）更少，而 JELN 中上调的 DE 基因（56%）和丰富的免疫/疾病途径（n=13）更多。免疫组织化学染色验证了骨髓细胞转录变化，MAPinf 和 MAPneg 奶牛的 IL 和 JE 组织以及引流的 LN 中 CD172 阳性骨髓细胞增加。与代谢相关的几个基因、GO 术语和途径在 IL 和 JE 中差异表达显著，但在 JELN 中程度较小（相对较少的代谢 GO 术语和途径富集），表明 MAP 感染后 IL 与 JE 和 JELN 之间存在明显的区域代谢变化。这些独特的组织和区域特异性差异为宿主对 MAP 感染的反应二分法提供了新的见解，这种二分法发生在慢性 MAP 感染奶牛的整个小肠和肠系膜 LN 中。
