Center for Gastrointestinal Biology and Disease, University of North Carolina and North Carolina State University, Chapel Hill and Raleigh, North Carolina.
Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Inflamm Bowel Dis. 2019 Apr 11;25(5):875-885. doi: 10.1093/ibd/izy386.
Adherent and invasive Escherichia coli (AIEC) is preferentially associated with ileal Crohn's disease (CD). The role of AIEC in the development of inflammation and its regional tropism is unresolved. The presence of long polar fimbriae (LPF) in 71% of ileal CD AIEC suggests a role for LPF in the tropism and virulence of AIEC. The aim of our study is to determine if AIEC, with or without LpfA, induces intestinal inflammation in monoassociated IL-10-/- mice.
We compared murine AIEC strains NC101 (phylogroup B2, LpfA-) and CUMT8 (phylogroup B1, LpfA+), and isogenic mutant CUMT8 lacking lpfA154, with a non-AIEC (E. coli K12), evaluating histologic inflammation, bacterial colonization, mucosal adherence and invasion, and immune activation.
IL-10-/- mice monoassociated with AIEC (either CUMT8, CUMT8:ΔlpfA, or NC101) but not K12 developed diffuse small intestinal and colonic inflammation. There was no difference in the magnitude and distribution of inflammation in mice colonized with CUMT8:ΔlpfA compared with wild-type CUMT8. Bacterial colonization was similar for all E. coli strains. Fluorescence in situ hybridization revealed mucosal adherence and tissue invasion by AIEC but not K12. Production of the cytokines IL-12/23 p40 by the intestinal tissue and IFN-γ and IL-17 by CD4 T cells correlated with inflammation.
IL-10-/- mice monoassociated with murine AIEC irrespective of LpfA expression developed chronic inflammation accompanied by IL-12/23 p40 production in the small and large intestines and IFN-γ/IL-17 production by CD4 T cells that model the interplay between enteric pathosymbionts, host susceptibility, and enhanced immune responses in people with IBD.
黏附侵袭性大肠杆菌（AIEC）与回肠克罗恩病（CD）密切相关。AIEC 在炎症发展及其区域嗜性中的作用尚未明确。71%回肠 CD AIEC 存在长极性菌毛（LPF），提示 LPF 在 AIEC 的嗜性和毒力中发挥作用。本研究旨在确定是否存在 AIEC（有无 LpfA）诱导单关联 IL-10-/-小鼠的肠道炎症。
我们比较了鼠源 AIEC 菌株 NC101（B2 群，LpfA-）和 CUMT8（B1 群，LpfA+），及其缺失 lpfA154 的同基因突变株 CUMT8:ΔlpfA，以及非 AIEC（大肠杆菌 K12），评估组织学炎症、细菌定植、黏膜黏附和侵袭以及免疫激活。
IL-10-/-小鼠单关联 AIEC（CUMT8、CUMT8:ΔlpfA 或 NC101）而不是 K12 会发展为弥漫性小肠和结肠炎症。与野生型 CUMT8 相比，CUMT8:ΔlpfA 定植的小鼠炎症程度和分布无差异。所有大肠杆菌菌株的细菌定植相似。荧光原位杂交显示 AIEC 但不是 K12 可黏附于黏膜并侵袭组织。肠道组织产生细胞因子 IL-12/23 p40，CD4 T 细胞产生 IFN-γ 和 IL-17，与炎症相关。
IL-10-/-小鼠单关联鼠源 AIEC（无论有无 LpfA 表达）均会发展为慢性炎症，伴有小肠和大肠中 IL-12/23 p40 的产生，以及 CD4 T 细胞中 IFN-γ/IL-17 的产生，模拟了肠共生病原体、宿主易感性和 IBD 患者增强的免疫反应之间的相互作用。
