Activation of type I interferon signaling in the parotid and exorbital lachrymal glands during the acute phase of encephalomyocarditis (EMC) virus infection in mice

作者：Ohguchi Atsuko^*; Yamauchi Hirofumi; Doi Kunio; Nakayama Hiroyuki

来源：Experimental and Molecular Pathology, 2016, 100(3): 434-440.

DOI：10.1016/j.yexmp.2016.03.007

• Encephalomyocarditis virus
• Parotid gland
• Exorbital lachrymal gland
• Type I interferon
• Mice

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 2 days post inoculation (DPI). The ratio of apoptotic acinar cells increased at 3 and 4 DPI. 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 3 DPI, and prominent acinar cell damage developed at 4 DPI. Viral RNA was detected at 3 and 4 DPI 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 2 DPI 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 2 DPI, 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 1 DPI, and became negative at 2 DPI. The weak- to strong-positive expression of IFNs at 1 DPI 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 2 DPI. 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.

• 出版日期2016-6