Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection.
Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection.
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DOI：
10.1084/jem.20070891
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发表时间：
2008-02-18
影响因子：
15.3
通讯作者：
Hussell, Tracy
中科院分区：
文献类型：
--
作者：
Didierlaurent, Arnaud;Goulding, John;Patel, Seema;Snelgrove, Robert;Low, Lionel;Bebien, Magali;Lawrence, Toby;van Rijt, Leonie S.;Lambrecht, Bart N.;Sirard, Jean-Claude;Hussell, Tracy
世界卫生组织估计，下呼吸道感染（不包括结核病）占传染病造成的所有死亡的35%。在许多情况下，死亡原因可能是由多种病原体引起的，例如，在感染流感病毒的患者中观察到的危及生命的细菌性肺炎。适应性免疫反应的标志是在每次连续遇到抗原时进化出更有效的免疫力。然而，在缺乏交叉反应性T和B细胞表位的情况下，一种肺部感染可以在较长的时间内改变下一种的免疫和病理。我们现在首次报道，这种现象是由肺哨兵细胞对Toll样受体（TLR）配体的持续脱敏介导的;这是一种在流感或呼吸道合胞病毒感染消退后持续数月的效应，与肺泡巨噬细胞中趋化因子产生和NF-κB活化减少有关。尽管这种脱敏可能有利于减轻整体免疫病理学，但减少的中性粒细胞募集与继发性呼吸道感染期间细菌负荷升高相关。因此，我们的数据表明，病毒后对TLR信号的脱敏可能是与大流行和季节性流感感染相关的常见继发性细菌性肺炎的一个可能的贡献者。
The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-κB activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection.
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DOI：
10.1016/s1473-3099(06)70466-2
发表时间：
2006-05
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Brundage JF
通讯作者：
Brundage JF
过敏原激发期间肺 CD11c+ 树突状细胞的体内耗竭消除了哮喘的特征。
DOI：
10.1084/jem.20042311
发表时间：
2005-03-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
van Rijt LS;Jung S;Kleinjan A;Vos N;Willart M;Duez C;Hoogsteden HC;Lambrecht BN
通讯作者：
Lambrecht BN
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
15.9
作者：
Andonegui, G;Bonder, CS;Kubes, P
通讯作者：
Kubes, P
DOI：
10.1073/pnas.0605200103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Feuillet, Vincent;Medjane, Samir;Alexopoulou, Lena
通讯作者：
Alexopoulou, Lena