Schäfer Alexander, Zani Laura, Pikalo Jutta, Hühr Jane, Sehl Julia, Mettenleiter Thomas C, Breithaupt Angele, Blome Sandra, Blohm Ulrike
Friedrich-Loeffler-Institut, Greifswald - Insel Riems, Germany.
Transbound Emerg Dis. 2021 Sep;68(5):2733-2749. doi: 10.1111/tbed.14048. Epub 2021 Mar 9.
Infection with African swine fever virus (ASFV) causes a highly lethal haemorrhagic disease in domestic and Eurasian wild pigs. Thus, it is a major threat to pig populations worldwide and a cause of substantial economic losses. Recently, less virulent ASFV strains emerged naturally, which showed higher experimental virulence in wild boar than in domestic pigs. The reason for this difference in disease progression and outcome is unclear but likely involves different immunological responses. Unfortunately, besides the importance of CD8α lymphocytes, little is known about the immune responses against ASFV in suids. Against this background, we used a multicolour flow cytometry platform to investigate the T-cell responses in wild boar and domestic pigs after infection with the moderately virulent ASFV strain 'Estonia2014' in two independent trials. CD4 /CD8α and CD4 /CD8α αβ T-cell frequencies increased in both subspecies in various tissues, but CD8α γδ T cells differentiated and responded in wild boar only. Proliferation in CD8α T cells was found 10 days post infectionem only. Frequencies of T-bet T cells increased in wild boar but not in domestic pigs. Of note, we found a considerable loss of perforin expression in cytotoxic T cells, 5 and 7 dpi. Both subspecies established a regulatory T-cell response 10 dpi. In domestic pigs, we show increasing levels of ICOS and CD8α invariant Natural Killer T cells. These disparities in T-cell responses might explain some of the differences in disease progression in wild boar and domestic pigs and should pave the way for future studies.
感染非洲猪瘟病毒(ASFV)会在家猪和欧亚野猪中引发一种高致死性出血性疾病。因此,它对全球猪群构成重大威胁,并造成巨大经济损失。最近,自然出现了毒性较低的ASFV毒株,这些毒株在野猪中的实验毒性高于家猪。疾病进展和结果存在这种差异的原因尚不清楚,但可能涉及不同的免疫反应。不幸的是,除了CD8α淋巴细胞的重要性外,关于猪对ASFV的免疫反应知之甚少。在此背景下,我们使用多色流式细胞术平台,在两项独立试验中研究了用中等毒性的ASFV毒株“爱沙尼亚2014”感染后野猪和家猪的T细胞反应。两个亚种的各种组织中CD4⁺/CD8α⁺和CD4⁺/CD8α⁻αβ T细胞频率均增加,但CD8α⁺γδ T细胞仅在野猪中分化并产生反应。仅在感染后10天发现CD8α⁺ T细胞增殖。T-bet⁺ T细胞频率在野猪中增加,而在家猪中未增加。值得注意的是,我们发现在感染后第5天和第7天,细胞毒性T细胞中的穿孔素表达大量丧失。两个亚种在感染后10天均建立了调节性T细胞反应。在家猪中,我们发现诱导共刺激分子(ICOS)和CD8α不变自然杀伤T细胞水平升高。T细胞反应的这些差异可能解释了野猪和家猪疾病进展中的一些差异,并应为未来的研究铺平道路。