Lu Shiou-Ling, Noda Takeshi
Center for Frontier Oral Sciences, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan.
Autophagy Rep. 2022 Oct 24;1(1):555-558. doi: 10.1080/27694127.2022.2137755. eCollection 2022.
Xenophagy is an intracellular defense mechanism against invading pathogens. (group A , GAS) is efficiently eliminated by this process in epithelial cells. However, we previously reported that the efficacy of xenophagy differs among cell types; intrinsic deficits in endothelial cell xenophagy failed to suppress GAS growth. Considering that the basal level of xenophagy is lower in endothelial cells as compared to epithelial cells, additional stimulation may be required to enhance this activity. Recently, we reported that VEGF (vascular endothelial growth factor) is the key factor facilitating xenophagy and lysosomal activity in endothelial cells. These processes further lead to the efficient killing of invading GAS. The cAMP-IP-Ca axis of the signaling pathway that activates TFEB (transcription factor EB) supports the transduction of the signal from VEGF. In addition, the severity of sepsis was observed to correlate with low VEGF concentrations in serum, both in a mouse model and in human patients. VEGF administration reduces mortality in a GAS sepsis model. Based on these findings, we propose that VEGF boosts the intracellular defense system of the endothelium by providing a strong blood vessel barrier to prevent bacterial dissemination.
异噬作用是一种针对入侵病原体的细胞内防御机制。A组链球菌（GAS）在此过程中可在上皮细胞中被有效清除。然而，我们之前报道过，异噬作用的效果在不同细胞类型中存在差异；内皮细胞异噬作用的内在缺陷无法抑制GAS的生长。鉴于与上皮细胞相比，内皮细胞中异噬作用的基础水平较低，可能需要额外的刺激来增强这种活性。最近，我们报道血管内皮生长因子（VEGF）是促进内皮细胞异噬作用和溶酶体活性的关键因子。这些过程进一步导致对入侵的GAS进行有效杀伤。激活转录因子EB（TFEB）的信号通路的cAMP-IP-Ca轴支持来自VEGF的信号转导。此外，在小鼠模型和人类患者中均观察到脓毒症的严重程度与血清中低浓度的VEGF相关。给予VEGF可降低GAS脓毒症模型中的死亡率。基于这些发现，我们提出VEGF通过提供强大的血管屏障来防止细菌扩散，从而增强内皮细胞的细胞内防御系统。
