Toll-like receptors (TLRs) are critical sensors for the detection of potentially harmful microbes. They are instrumental in initiating innate and adaptive immune responses against pathogenic organisms. However, exaggerated activation of TLR receptor signaling can also be responsible for the onset of autoimmune and inflammatory diseases. While positive regulators of TLR signaling, such as protein serine/threonine kinases, have been studied intensively, only little is known about phosphatases, which counterbalance and limit TLR signaling. In this review, we summarize protein phosphorylation events and their roles in the TLR pathway and highlight the involvement of protein phosphatases as negative regulators at specific steps along the TLR-initiated signaling cascade. Then, we focus on individual phosphatase families, specify the function of individual enzymes in TLR signaling in more detail and give perspectives for future research. A better understanding of phosphatase-mediated regulation of TLR signaling could provide novel access points to mitigate excessive immune activation and to modulate innate immune signaling.

中文翻译：

---

TLR 信号中的蛋白磷酸酶

Toll 样受体 (TLR) 是检测潜在有害微生物的关键传感器。它们有助于启动针对病原生物的先天性和适应性免疫反应。然而，过度激活 TLR 受体信号也可能导致自身免疫性疾病和炎症性疾病的发生。虽然已经深入研究了 TLR 信号传导的正调节因子，例如蛋白质丝氨酸/苏氨酸激酶，但对平衡和限制 TLR 信号传导的磷酸酶知之甚少。在这篇综述中，我们总结了蛋白质磷酸化事件及其在 TLR 通路中的作用，并强调了蛋白质磷酸酶作为负调节因子参与 TLR 启动的信号级联的特定步骤。然后，我们关注个别的磷酸酶家族，更详细地说明单个酶在 TLR 信号传导中的功能，并为未来的研究提供展望。更好地理解磷酸酶介导的 TLR 信号调节可以提供新的途径来减轻过度免疫激活和调节先天免疫信号。