Ohguchi Atsuko, Yamauchi Hirofumi, Doi Kunio, Nakayama Hiroyuki
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
Exp Mol Pathol. 2016 Jun;100(3):434-40. doi: 10.1016/j.yexmp.2016.03.007. Epub 2016 Apr 11.
The present study was carried out to clarify the mechanisms of EMC virus-induced sialodacryoadenitis in mice during the acute phase infection focusing on the activation of type I interferon (IFN) signaling in the parotid and exorbital lachrymal glands. In the parotid gland, a few apoptotic acinar cells were detected at 2days post inoculation (DPI). The ratio of apoptotic acinar cells increased at 3 and 4DPI. On the other hand, in the exorbital lachrymal gland, apoptosis of acinar cells and infiltration of inflammatory cells mainly composed of mononuclear cells started at 3DPI, and prominent acinar cell damage developed at 4DPI. Viral RNA was detected at 3 and 4DPI in both glands and the expression level was higher in the exorbital lachrymal gland than in the parotid gland. The up-regulation of IFN-stimulated genes (ISGs), such as Irf7, Pkr and Oas, was quickly induced at 2DPI in the parotid gland, and this probably contributed to suppress viral replication and to eliminate affected cells by apoptosis. In the exorbital lachrymal gland, the expression levels of ISGs mRNAs were not elevated at 2DPI, suggesting no induction of an effective anti-viral response such as apoptosis at this time point. In the exorbital lachrymal gland, the mRNA expression of IFN beta and IFN alpha (type I IFNs) was weak- to strong-positive at 1DPI, and became negative at 2DPI. The weak- to strong-positive expression of IFNs at 1DPI is likely related to the abrupt viral replication and pathological changes in the exorbital lachrymal gland through activating the negative feedback regulation that depressed the IFN signaling cascade at 2DPI. In conclusion, the present study showed the changes in factors involved in the activation of type I IFN signaling cascade in the parotid and exorbital lachrymal glands and their differences between the two glands during the acute phase of EMC virus infection in mice.
本研究旨在阐明鼠脑心肌炎病毒（EMC病毒）感染小鼠急性期引起涎泪腺炎的机制，重点关注腮腺和眶泪腺中I型干扰素（IFN）信号的激活情况。在腮腺中，接种后2天（DPI）检测到少数凋亡的腺泡细胞。凋亡腺泡细胞的比例在3和4 DPI时增加。另一方面，在眶泪腺中，腺泡细胞凋亡和主要由单核细胞组成的炎性细胞浸润在3 DPI时开始，4 DPI时出现明显的腺泡细胞损伤。在两个腺体的3和4 DPI时均检测到病毒RNA，且其在眶泪腺中的表达水平高于腮腺。腮腺中在2 DPI时迅速诱导了干扰素刺激基因（ISGs）如Irf7、Pkr和Oas的上调，这可能有助于抑制病毒复制并通过凋亡消除受影响的细胞。在眶泪腺中,2 DPI时ISGs mRNA的表达水平未升高，表明此时未诱导有效的抗病毒反应如凋亡。在眶泪腺中，IFNβ和IFNα（I型干扰素）的mRNA表达在1 DPI时为弱阳性至强阳性，在2 DPI时变为阴性。1 DPI时IFN的弱阳性至强阳性表达可能与眶泪腺中病毒的突然复制和病理变化有关，通过激活负反馈调节在2 DPI时抑制了IFN信号级联反应。总之，本研究显示了小鼠EMC病毒感染急性期腮腺和眶泪腺中I型干扰素信号级联激活相关因子的变化以及两个腺体之间的差异。
