A regulatory role for macrophage class A scavenger receptors in TLR4-mediated LPS responses
A regulatory role for macrophage class A scavenger receptors in TLR4-mediated LPS responses
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DOI：
10.1002/eji.200939891
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Karlsson, Mikael C. I.
中科院分区：
文献类型：
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作者：
Chen, Yunying;Wermeling, Fredrik;Karlsson, Mikael C. I.
TLR是感染的关键传感器，其对微生物组分的识别导致炎症反应的诱导。我们发现，在体内，TLR 4参与LPS诱导上调A类清道夫受体（SR）巨噬细胞受体与胶原结构（MARCO）和SR-A，这发生，至少在MARCO的情况下，通过MyD 88依赖性和非依赖性途径。当用低剂量LPS接着高剂量LPS攻击小鼠时，A类SR缺陷小鼠显示出比WT小鼠更高的存活率。这与IL-10和抗LPS Ab的产生增加以及边缘区B细胞的活化状态增加配对。然而，当用脑膜炎奈瑟氏菌或单核细胞增生李斯特菌腹腔内攻击小鼠时，受体对存活并不重要，但发现它们有助于微生物的捕获和清除。这表明在细菌感染的早期阶段A类SR的上调具有生理意义。因此，我们相信我们已经揭示了SR调节免疫系统激活状态的机制，并参与平衡对感染的适当免疫反应。这种调节在维持耐受性方面也很重要，因为这些受体已被证明参与调节自身反应性。
Recognition of microbial components by TLR, key sensors of infection, leads to induction of inflammatory responses. We found that, in vivo, TLR4 engagement by LPS induces up-regulation of the class A scavenger receptors (SR) macrophage receptor with a collagenous structure (MARCO) and SR-A, which occurs, at least in the case of MARCO, via both MyD88-dependent and -independent pathways. When challenging mice with a low dose of LPS followed by a high dose, class A SR-deficient mice showed a higher survival rate than WT mice. This was paired with increased production of IL-10 and anti-LPS Ab, as well as increased activation status of marginal zone B cells. However, the receptors were not crucial for survival when challenging mice i.p. with Neisseria meningitidis or Listeria monocytogenes, but they were found to contribute to microbial capture and clearance. This indicates physiological significance for the up-regulation of class A SR during early stages of bacterial infection. Thus, we believe that we have revealed a mechanism where SR regulate the activation status of the immune system and are involved in balancing a proper immune response to infection. This regulation could also be important in maintaining tolerance since these receptors have been shown to be involved in regulation of self-reactivity.