Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; Department of Silviculture and Agro-forestry, Dr. Y.S. Parmar University of Horticulture and Forestry, Nauni, Solan, Himachal Pradesh, India.
Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; Department of Virology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey.
Cell Immunol. 2021 Dec;370:104450. doi: 10.1016/j.cellimm.2021.104450. Epub 2021 Oct 14.
Infection of the cornea with HSV results in an immune-inflammatory reaction orchestrated by proinflammatory T cells that is a major cause of human vision impairment. The severity of lesions can be reduced if the representation of inflammatory T cells is changed to increase the presence of T cells with regulatory function. This report shows that inhibiting glutamine metabolism using 6-Diazo-5-oxo-l-norleucine (DON) administered via intraperitoneal (IP) starting 6 days after ocular infection and continued until day 15 significantly reduced the severity of herpetic stromal keratitis lesions. The therapy resulted in reduced neutrophils, macrophages as well proinflammatory CD4 Th1 and Th17 T cells in the cornea, but had no effect on levels of regulatory T cells. A similar change in the representation of inflammatory and regulatory T cells occurred in the trigeminal ganglion (TG) the site where HSV infection establishes latency. Glutamine metabolism was shown to be required for the in-vitro optimal induction of both Th1 and Th17 T cells but not for the induction of Treg that were increased when glutamine metabolism was inhibited. Inhibiting glutamine metabolism also changed the ability of latently infected TG cells from animals previously infected with HSV to reactivate and produce infectious virus.
单纯疱疹病毒（HSV）感染角膜会引发由促炎 T 细胞介导的免疫炎症反应，这是导致人类视力损害的主要原因。如果能改变炎症性 T 细胞的表型，增加具有调节功能的 T 细胞的存在，就能减轻病变的严重程度。本报告表明，通过腹腔内（IP）注射 6-二氮-5-氧-正亮氨酸（DON），从眼部感染后 6 天开始给药，并持续至第 15 天，可以抑制谷氨酰胺代谢，从而显著减轻单纯疱疹性基质角膜炎病变的严重程度。该疗法减少了角膜中的中性粒细胞、巨噬细胞以及促炎 CD4 Th1 和 Th17 T 细胞，但对调节性 T 细胞的水平没有影响。在三叉神经节（TG）——HSV 感染潜伏的部位，也出现了类似的炎症和调节性 T 细胞表型的变化。谷氨酰胺代谢是体外诱导 Th1 和 Th17 T 细胞的最佳条件，但不是诱导 Treg 的最佳条件，当抑制谷氨酰胺代谢时，Treg 会增加。抑制谷氨酰胺代谢也改变了先前感染 HSV 的动物潜伏感染 TG 细胞重新激活并产生感染性病毒的能力。
