Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Eur J Immunol. 2010 May;40(5):1451-60. doi: 10.1002/eji.200939891.
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.
TLR 是感染的关键传感器，可识别微生物成分，从而引发炎症反应。我们发现，在体内，LPS 通过 TLR4 结合诱导具有胶原结构的 A 类清道夫受体（MARCO）和 SR-A 的上调，至少在 MARCO 的情况下，该过程通过 MyD88 依赖性和非依赖性途径发生。用低剂量 LPS 攻击小鼠，然后再用高剂量 LPS 攻击时，A 类 SR 缺陷型小鼠的存活率高于 WT 小鼠。这与 IL-10 和抗 LPS Ab 的产生增加以及边缘区 B 细胞的激活状态增加有关。然而，当用脑膜炎奈瑟球菌或李斯特菌攻击小鼠时，这些受体对于生存并不是至关重要的，但它们被发现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，我们认为我们已经揭示了一种机制，即 SR 调节免疫系统的激活状态，并参与平衡对感染的适当免疫反应。这种调节在维持耐受方面也可能很重要，因为这些受体已被证明参与自身反应的调节。
