TLR2, but not TLR4, is required for effective host defence against Chlamydia respiratory tract infection in early life.
TLR2, but not TLR4, is required for effective host defence against Chlamydia respiratory tract infection in early life.
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DOI：
10.1371/journal.pone.0039460
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hansbro PM
中科院分区：
文献类型：
--
作者：
Beckett EL;Phipps S;Starkey MR;Horvat JC;Beagley KW;Foster PS;Hansbro PM
肺炎衣原体通常导致儿童呼吸道感染，流行病学调查强烈地将感染与哮喘的发病机制联系在一起。早期生命的免疫系统是不成熟的，可能对病原体没有适当的反应。Toll样受体2和4被认为是感知细菌的主要模式识别受体，但它们在生命早期对先天免疫和获得性免疫的作用尚不清楚。我们研究了TLR2和4在新生野生型(Wt)或TLR2缺陷(−/−)、4−/−或2/4−/−BALB/c小鼠诱导对衣原体呼吸道感染的免疫应答中的作用。WT小鼠有中度疾病和感染。与其他组相比，TLR2−/−小鼠的病情更严重，感染更严重和持续时间更长。TLR4−/−小鼠无症状。TLR2/4−/−小鼠有严重的早期疾病和持续感染，此后症状消失，与TLR4−/−小鼠没有症状一致。WT小鼠通过自然杀伤(NK)细胞、中性粒细胞、髓样细胞(MDCS)和浆细胞样(PDCs)树突状细胞的涌入，并激活CD4+和CD8+T细胞进入肺部，从而产生强大的先天和适应性反应。WT小鼠也能有效地在淋巴结和肺内产生干扰素γ，并能促进淋巴结T细胞的增殖。−/−小鼠先天(尤其是中性粒细胞)、适应性细胞反应和IL-17表达增强，但干扰素γ反应和T细胞增殖能力下降。TLR2/4−/−小鼠先天反应和适应性反应减弱。最重要的是，在缺乏TLR2的情况下，中性粒细胞的吞噬功能受损。因此，TLR2的表达，特别是在中性粒细胞上的表达，对于有效控制早期生命中的衣原体呼吸道感染是必要的。失去对感染的控制会导致增强但无效的TLR4介导性炎症反应，从而延长疾病症状。这表明TLR2激动剂在治疗早期衣原体感染和相关疾病方面可能是有益的。
Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.
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影响因子：
6.7
作者：
Asquith KL;Horvat JC;Kaiko GE;Carey AJ;Beagley KW;Hansbro PM;Foster PS
通讯作者：
Foster PS
影响因子：
20.3
作者：
Hayashi, F;Means, TK;Luster, AD
通讯作者：
Luster, AD
影响因子：
4.4
作者：
Adkins, P;Bu, YR;Guevara, P
通讯作者：
Guevara, P
影响因子：
3.4
作者：
Luther, Kathrin;Torosantucci, Antonella;Ebel, Frank
通讯作者：
Ebel, Frank
影响因子：
13.5
作者：
Hansbro NG;Horvat JC;Wark PA;Hansbro PM
通讯作者：
Hansbro PM