Queensland Institute of Medical Research and the Australian Centre for Vaccine Development, Herston, Queensland, Australia.
PLoS Pathog. 2011 Oct;7(10):e1002279. doi: 10.1371/journal.ppat.1002279. Epub 2011 Oct 6.
LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.
LIGHT（TNFSF14）是参与炎症和抗感染防御的 TNF 超家族的一员。LIGHT 通过两种细胞结合受体；疱疹病毒进入介体（HVEM）和淋巴毒素-β受体（LTβR）发出信号。我们发现，在感染原生动物寄生虫利什曼原虫引起的内脏利什曼病（VL）的小鼠中，LIGHT 对于控制肝寄生虫生长至关重要。LIGHT-HVEM 信号对于早期树突状细胞 IL-12/IL-23p40 的产生以及产生 IFNγ 和 TNF 的 T 细胞的生成至关重要，这些 T 细胞可控制肝感染。但是，我们还发现，LIGHT-LTβR 相互作用通过限制 CD4(+) T 细胞功能和 TNF 依赖性杀菌机制的机制，在感染的前 7 天内抑制肝脏中的抗寄生虫免疫。因此，我们已经确定了 LIGHT 在感染中的不同作用，并表明操纵 LIGHT 与其受体之间的相互作用可能用于治疗优势。
