Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide

Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide
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通过口服抗菌药物根除肠道共生菌群会干扰宿主对脂多糖的反应

DOI:
10.1007/s10096-010-0905-3
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发表时间:
2010
影响因子:
4.5
通讯作者:
Jiro Imanishi
Jiro Imanishi
中科院分区:
医学3区
文献类型:
--
作者:
T. Umenai;Hideyo Hirai;Nobuaki Shime;Takaaki Nakaya;T. Asahara;Koji Nomoto;Masakazu Kita;Yoshifumi Tanaka;Jiro Imanishi

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肠道微环境的宿主成分和共生微生物在宿主防御的形成和维持中发挥作用。最近的观察表明,Toll样受体(TLRs)参与了对肠道微生物的天然免疫识别。然而,关于TLR在肠道微生物维持系统宿主防御中的作用,人们知之甚少。我们研究了小鼠口服链霉素和头孢噻肟3周后,TLR4和TLR2在小鼠肺泡巨噬细胞和腹膜巨噬细胞上的表达和功能。经积极治疗后,肠道微生物基本被消灭,巨噬细胞表面TLR4和TLR2的表达明显下调。当主动治疗的小鼠受到TLR4配体脂多糖(LPS)的攻击时,宿主的反应明显受损。我们的结果表明,口服抗菌药下调了巨噬细胞表面TLR的表达,并通过改变肠道环境来调节宿主对内毒素的免疫反应。
The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.
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