Zhu James J, Stenfeldt Carolina, Bishop Elizabeth A, Canter Jessica A, Eschbaumer Michael, Rodriguez Luis L, Arzt Jonathan
Foreign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Orient, NY 11957, USA.
Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66506, USA.
Pathogens. 2022 Jul 22;11(8):822. doi: 10.3390/pathogens11080822.
Foot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the analysis of differentially expressed genes (DEG) identified during the transitional phase of infection, defined as the period when animals diverge between becoming carriers or terminators. During this phase, Th17-stimulating cytokines (IL6 and IL23A) and Th17-recruiting chemokines (CCL14 and CCL20) were upregulated in animals that were still infected (transitional carriers) compared to those that had recently cleared infection (terminators), whereas chemokines recruiting neutrophils and CD8+ T effector cells (CCL3 and ELR+CXCLs) were downregulated. Upregulated Th17-specific receptor, CCR6, and Th17-associated genes, CD146, MIR155, and ThPOK, suggested increased Th17 cell activity in transitional carriers. However, a complex interplay of the Th17 regulatory axis was indicated by non-significant upregulation of IL17A and downregulation of IL17F, two hallmarks of TH17 activity. Other DEG suggested that transitional carriers had upregulated aryl hydrocarbon receptor (AHR), non-canonical NFκB signaling, and downregulated canonical NFκB signaling. The results described herein provide novel insights into the mechanisms of establishment of FMDV persistence. Additionally, the fact that ruminants, unlike pigs, produce a large amount of AHR ligands suggests a plausible explanation of why FMDV persists in ruminants, but not in pigs.
口蹄疫病毒（FMDV）可在反刍动物的咽部上皮中持续感染，但在猪中不会。我们之前的研究表明，牛的FMDV持续感染与几种招募免疫细胞的趋化因子表达不足有关。本报告重点分析了在感染过渡阶段鉴定出的差异表达基因（DEG），该阶段定义为动物在成为携带者或清除者之间分化的时期。在此阶段，与近期清除感染的动物（清除者）相比，仍被感染的动物（过渡携带者）中刺激Th17的细胞因子（IL6和IL23A）以及招募Th17的趋化因子（CCL14和CCL20）上调，而招募中性粒细胞和CD8 + T效应细胞的趋化因子（CCL3和ELR + CXCLs）下调。上调的Th17特异性受体CCR6以及与Th17相关的基因CD146、MIR155和ThPOK表明过渡携带者中Th17细胞活性增加。然而，IL17A的非显著上调和IL17F的下调这两个TH17活性的标志表明Th17调节轴存在复杂的相互作用。其他DEG表明过渡携带者的芳烃受体（AHR）、非经典NFκB信号上调，经典NFκB信号下调。本文所述结果为FMDV持续感染建立机制提供了新见解。此外，与猪不同，反刍动物会产生大量AHR配体这一事实，为FMDV为何在反刍动物中持续感染而在猪中不会提供了一个合理的解释。
