缺乏核苷酸寡聚化结构域2的常规定殖小鼠的感染
infection of conventionally colonized mice lacking nucleotide-oligomerization-domain-2.
作者信息
Bereswill Stefan, Grundmann Ursula, Alutis Marie E, Fischer André, Heimesaat Markus M
机构信息
Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
出版信息
Gut Pathog. 2017 Jan 21;9:5. doi: 10.1186/s13099-017-0155-3. eCollection 2017.
BACKGROUND
The nucleotide-binding oligomerisaton protein 2 (NOD2) constitutes a pivotal sensor of bacterial muramyl dipeptide and assures expression of distinct antimicrobial peptides and mediators produced by enterocytes and immune cells directed against pathogens including . We here elucidated the role of NOD2 during murine infection in more detail.
RESULTS
Conventionally colonized NOD2 deficient (NOD2) mice and corresponding wildtype (WT) counterparts were perorally infected with strain 81-176 on three consecutive days. The pathogen colonized both WT and NOD2 mice only sporadically until day 14 post infection (p.i.). However, the slightly higher prevalence of in NOD2 mice was accompanied by higher intestinal loads known to facilitate colonization. Neither overt macroscopic (clinical) nor microscopic sequelae (such as colonic epithelial apoptosis) could be observed upon murine infection of either genotype. Innate immune responses were less distinctly induced in infected NOD2 versus WT mice as indicated by lower colonic numbers of neutrophils in the former. Conversely, adaptive immune cell counts including T lymphocytes were higher in large intestines of NOD2 as compared to WT mice that were paralleled by increased colonic IL-6 secretion and higher TNF and IL-18 mRNA expression levels in large intestines of the former. Only in NOD2 mice, however, colonic IL-22 mRNA expression was down-regulated at day 14 p.i. Whereas viable commensal intestinal bacteria could exclusively be detected in mesenteric lymph nodes and livers of NOD2 mice, bacterial translocation rates to kidneys and spleen were NOD2 independent. Notably, large intestinal mRNA expression levels of mucin-2, constituting a pivotal factor involved in epithelial barrier integrity, were comparable in naive and infected mice of either genotype.
CONCLUSION
NOD2 is involved in the well-balanced regulation of innate and adaptive pro-inflammatory immune responses of conventional mice upon infection.
背景
核苷酸结合寡聚化结构域蛋白2（NOD2）是细菌胞壁酰二肽的关键传感器，可确保肠上皮细胞和免疫细胞产生的针对包括……在内的病原体的不同抗菌肽和介质的表达。我们在此更详细地阐明了NOD2在小鼠感染过程中的作用。
结果
连续三天经口用81 - 176菌株感染常规定殖的NOD2缺陷（NOD2）小鼠和相应的野生型（WT）对照小鼠。在感染后第14天（p.i.）之前，病原体仅偶尔定殖于WT和NOD2小鼠。然而，NOD2小鼠中略高的患病率伴随着已知有利于定殖的更高肠道负荷。在感染任一基因型小鼠后，均未观察到明显的宏观（临床）或微观后遗症（如结肠上皮细胞凋亡）。如前一组小鼠结肠中中性粒细胞数量较低所示，与WT小鼠相比，感染的NOD2小鼠中先天免疫反应诱导不明显。相反，与WT小鼠相比，NOD2小鼠大肠中包括T淋巴细胞在内的适应性免疫细胞计数更高，这与前一组小鼠结肠中IL - 6分泌增加以及大肠中TNF和IL - 18 mRNA表达水平升高平行。然而，仅在NOD2小鼠中，感染后第14天结肠IL - 22 mRNA表达下调。虽然仅在NOD2小鼠的肠系膜淋巴结和肝脏中可检测到活的共生肠道细菌，但向肾脏和脾脏的细菌易位率与NOD2无关。值得注意的是，构成上皮屏障完整性关键因素的粘蛋白2的大肠mRNA表达水平在任一基因型的未感染和感染小鼠中相当。
结论
NOD2参与常规小鼠感染后先天和适应性促炎免疫反应的平衡调节。
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