Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection.

Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection.
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抗生素对咽部微生物群的破坏促进呼吸道合胞病毒感染后气道高反应性

DOI:
10.1371/journal.pone.0041104
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Liu E
Liu E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ni K;Li S;Xia Q;Zang N;Deng Y;Xie X;Luo Z;Luo Y;Wang L;Fu Z;Liu E

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背景调节性T细胞(Treg细胞)在呼吸道合胞病毒(RSV)感染的免疫应答中起着重要的调节作用,是咽部共生肺炎球菌的促进剂。抗生素对呼吸道合胞病毒感染后呼吸道反应性和相关免疫反应的影响尚不清楚。方法3周龄雌性BALB/c小鼠感染呼吸道合胞病毒(RSV)后,于感染后1d开始口服抗生素或双蒸水(DdH2O)。观察用药后7d和14d咽部菌群的变化,在用药后8d和15d取肺泡灌洗液(BALF)中的炎性细胞,结合肺组织病理学、气道高反应性(AHR)、肺和脾Treg细胞反应等指标进行检测。15d后检测肺组织Foxp3mRNA表达、肺泡灌洗液和肺组织匀浆中IL-10和转化生长因子-β-1的表达。用卵白蛋白(OVA)攻击诱导RSV感染后的AHR。结果用抗生素治疗7d后,咽部共生链球菌基本清除,用药14d后也有同样的变化,RSV感染后15d用抗生素治疗可促进AHR。肺组织Treg细胞、Foxp3m RNA和转化生长因子-β-1同步减少。在OVA攻击下也观察到了类似的结果。结论呼吸道合胞病毒感染后,抗生素治疗可清除咽部共生菌如链球菌,从而诱发AHR,减少肺Treg细胞。
Background Regulatory T cells (Treg cells), which are essential for regulation of immune response to respiratory syncytial virus (RSV) infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified. Methods Female BALB/c mice (aged 3 weeks) were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH2O) from 1 d post infection (pi). Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF) were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR), pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA) challenge was used to induce AHR after RSV infection. Results The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under OVA challenge. Conclusions After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.
DOI: 10.1086/592714
发表时间: 2008-11-15
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