A regulatory role for interleukin 4 in differential inflammatory responses in the lung following infection of mice primed with Th1-or Th2-inducing pertussis vaccines
A regulatory role for interleukin 4 in differential inflammatory responses in the lung following infection of mice primed with Th1-or Th2-inducing pertussis vaccines
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DOI：
10.1128/iai.68.3.1383-1390.2000
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发表时间：
2000-03-01
影响因子：
3.1
通讯作者：
Mills, KHG
中科院分区：
文献类型：
--
作者：
McGuirk, P;Mills, KHG
粘膜表面对感染性病原体的保护依赖于局部抗体应答、炎症介质的产生和免疫效应细胞向感染部位的募集。由于Th 1和Th 2细胞产生具有促炎和抗炎活性的细胞因子，因此用诱导这些T细胞亚型的疫苗免疫可以调节随后对感染的炎症反应。我们已经证明，百日咳全细胞或无细胞疫苗（Pw或Pa）的小鼠免疫选择性诱导Th 1和Th 2细胞，分别。在这项研究中，我们已经使用了一个小鼠的寄生虫感染模型，以证明与Th 1或Th 2诱导百日咳疫苗的启动可以影响局部炎症反应和免疫效应细胞在肺部后的气雾剂挑战与百日咳杆菌。分析B过程中采集的支气管肺泡灌洗液（BAL）。未感染百日咳的小鼠或用Pw免疫的小鼠的百日咳感染揭示了中性粒细胞的早期流入和肺中白细胞介素1 β（IL-1 β）的局部产生。相反，在用Th 2诱导Pa免疫的小鼠攻击后，未观察到中性粒细胞浸润和IL-1 β产生。相反，在感染过程中，局部产生的IL-6和IL-1 ra是显着更大的PA免疫小鼠比那些免疫Pw。对基因敲除小鼠的研究显示，B治疗后肺中出现中性粒细胞和淋巴细胞浸润。IL-4缺陷型（IL-4（-/-））小鼠的百日咳感染，但在用Pa.此外，PA免疫的IL-4（-/-）小鼠中IL-1 β、IL-6和IL-1 ra的水平与Pw免疫的小鼠中的水平相当。这些结果表明，在用B攻击后，Th 1-和Th 2-诱导疫苗对肺中的保护性炎症反应具有不同的影响。百日咳和牵连IL-4作为一个重要的调节炎症细胞募集。
Protection against infectious pathogens at mucosal surfaces is dependent on local antibody responses, production of inflammatory mediators, and recruitment of immune effector cells to the site of infection. Since Th1 and Th2 cells produce cytokines with pro- and anti-inflammatory activities, immunization with vaccines that induce these T-cell subtypes may regulate the subsequent inflammatory response to infection. We have demonstrated that immunization of mice with pertussis whole-cell or acellular vaccines (Pw or Pa) selectively induces Th1 and Th2 cells, respectively. In this study we have used a murine respiratory-infection model to demonstrate that priming with a Th1- or Th2-inducing pertussis vaccine can influence the local inflammatory response and immune effector cells in the lung following aerosol challenge with Bordetella pertussis. Analysis of bronchoalveolar lavage (BAL) fluid taken during the course of B. pertussis infection of naive mice or mice immunized with Pw revealed an early influx of neutrophils and local production of interleukin 1 beta (IL-1 beta) in the lungs. In contrast, neutrophil infiltration and IL-1 beta production were not observed following challenge of mice immunized with the Th2-inducing Pa. Conversely, during infection local production of IL-6 and IL-1ra was significantly greater in mice immunized with Pa than in those immunized with Pw. Studies of knockout mice revealed neutrophil and lymphocyte infiltration in the lungs following B. pertussis infection of IL-4-defective (IL-4(-/-)) mice but not in wild-type mice immunized with Pa. Furthermore, the levels of IL-1 beta, IL-6, and IL-1ra in Pa-immunized IL-4(-/-) mice were comparable to those in mice immunized with Pw. These results demonstrate distinct influences of Th1- and Th2-inducing vaccines on the protective inflammatory responses in the lungs following challenge with B. pertussis and implicate IL-4 as an important regulator of inflammatory-cell recruitment.