Malbon A J, Meli M L, Barker E N, Davidson A D, Tasker S, Kipar A
Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Switzerland; Graduate School for Cellular and Biomedical Sciences, Bern, Switzerland; Center for Clinical Studies, Switzerland.
Center for Clinical Studies, Switzerland; Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Switzerland.
J Comp Pathol. 2019 Jan;166:69-86. doi: 10.1016/j.jcpa.2018.11.001. Epub 2018 Dec 17.
Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response. Natural initial enteric FCoV infection may remain subclinical, or result in mild enteric signs or the development of FIP; cats may also carry the virus systemically with no adverse effect. This study screened mesenteric lymph nodes (MLNs), the presumed first site of FCoV spread from the intestine regardless of viraemia, for changes in the transcription of a panel of innate immune response mediators in response to systemic FCoV infection and with FIP, aiming to identify key pathways triggered by FCoV. Cats with and without FIP, the latter with and without FCoV infection in the MLN, were compared. Higher expression levels in FIP were found for toll-like receptors (TLRs) 2, 4 and 8. These are part of the first line of defence and suggest a response to both viral structural proteins and viral nucleic acid. Expression of genes encoding inflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-6, IL-15, tumour necrosis factor (TNF)-α, CXCL10, CCL8, interferon (IFN)-α, IFN-β and IFN-γ, was higher in cats with FIP, consistent with inflammatory pathway activation. Expression of genes encoding transcription factors STAT1 and 2, regulating signalling pathways, particularly of the interferons, was also higher. Among cats without FIP, there were few differences between virus-positive and virus-negative MLNs; however, TLR9 and STAT2 expression were higher with infection, suggesting a direct viral effect. The study provides evidence for TLR involvement in the response to FCoV. This could open up new avenues for therapeutic approaches.
猫传染性腹膜炎（FIP）是一种几乎总是致命的由猫冠状病毒（FCoV）引起的疾病，被认为是病毒突变和过度活跃的免疫反应共同作用的结果。自然状态下，最初的肠道FCoV感染可能没有临床症状，或者导致轻微的肠道症状或FIP的发生；猫也可能全身性携带该病毒而没有不良影响。本研究对肠系膜淋巴结（MLNs）进行了筛查，无论是否存在病毒血症，MLNs被认为是FCoV从肠道传播的首个部位，以检测一组先天免疫反应介质在全身性FCoV感染及FIP情况下转录的变化，旨在确定由FCoV触发的关键途径。对患有和未患有FIP的猫进行了比较，后者的MLN中有或没有FCoV感染。在FIP中发现Toll样受体（TLRs）2、4和8的表达水平较高。这些是第一道防线的一部分，表明对病毒结构蛋白和病毒核酸均有反应。在患有FIP的猫中，编码炎性细胞因子和趋化因子的基因表达较高，包括白细胞介素（IL）-1β、IL-6、IL-15、肿瘤坏死因子（TNF）-α、CXCL10、CCL8、干扰素（IFN）-α、IFN-β和IFN-γ，这与炎症途径的激活一致。编码转录因子STAT1和2的基因表达也较高，它们调节信号通路，特别是干扰素的信号通路。在没有FIP的猫中，病毒阳性和病毒阴性的MLN之间几乎没有差异；然而，感染时TLR9和STAT2的表达较高，表明病毒有直接作用。该研究为TLRs参与对FCoV的反应提供了证据。这可能为治疗方法开辟新途径。
