衍生的脂磷寡糖通过 TLR1/2 诱导血小板活化和 DKK1 产生来影响宿主的早期免疫反应。

BACKGROUND: Platelets are rapidly deployed to infection sites and respond to pathogenic molecules via pattern recognition receptors (TLR, NLRP). Dickkopf1 (DKK1) is a quintessential Wnt antagonist produced by a variety of cell types including platelets, endothelial cells, and is known to modulate pro-inflammatory responses in infectious diseases and cancer. Moreover, DKK1 is critical for forming leukocyte-platelet aggregates and induction of type 2 cell-mediated immune responses. Our previous publication showed activated platelets release DKK1 following recognition. RESULTS: Here we probed the role of the key surface virulence glycoconjugate lipophosphoglycan (LPG), on DKK1 production using null mutants deficient in LPG synthesis ( and ). -induced DKK1 production was reduced to control levels in the absence of LPG in both mutants and was restored upon re-expression of the cognate or genes. Furthermore, the formation of leukocyte-platelet aggregates was dependent on LPG. LPG mediated platelet activation and DKK1 production occurs through TLR1/2. CONCLUSION: Thus, LPG is a key virulence factor that induces DKK1 production from activated platelets, and the circulating DKK1 promotes Th2 cell polarization. This suggests that LPG-activated platelets can drive innate and adaptive immune responses to infection.

背景：血小板迅速被部署到感染部位，并通过模式识别受体（TLR、NLRP）对病原体分子做出反应。Dickkopf1（DKK1）是一种Wnt 拮抗剂，由多种细胞类型产生，包括血小板、内皮细胞，已知可调节感染性疾病和癌症中的促炎反应。此外，DKK1 对于形成白细胞-血小板聚集和诱导 2 型细胞介导的免疫反应至关重要。我们之前的研究表明，激活的血小板在识别后释放 DKK1。

结果：在这里，我们利用缺乏 LPG 合成的缺失突变体（和）来探究关键表面毒力糖缀合物脂磷壁酸（LPG）在 DKK1 产生中的作用。在没有 LPG 的情况下，和突变体中的 DKK1 产生均降低至对照水平，并且在重新表达相应的或基因时恢复。此外，白细胞-血小板聚集的形成依赖于 LPG。LPG 通过 TLR1/2 介导血小板激活和 DKK1 产生。

结论：因此，LPG 是一种关键的毒力因子，可诱导激活的血小板产生 DKK1，而循环中的 DKK1 促进 Th2 细胞极化。这表明 LPG 激活的血小板可以驱动对感染的先天和适应性免疫反应。