Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia.
Commonwealth Scientific and Industrial Research Organisation Health and Biosecurity, Australian Centre for Disease Prevention, East Geelong, VIC, Australia.
Front Immunol. 2020 Sep 24;11:559113. doi: 10.3389/fimmu.2020.559113. eCollection 2020.
As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8 T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model.
正如最近 SARS-CoV-2 的爆发所强调的那样,人畜共患病毒(如致命的甲型流感 A/H7N9 病毒亚型)引发大流行的威胁仍然是一个主要的全球健康关注点。与天然禽宿主相比,H7N9 病毒株在哺乳动物宿主中似乎表现出更高的疾病严重程度,尽管其确切机制尚不清楚。对 H7N9 宿主-病原体相互作用的了解主要局限于自然散发的人类感染。为了阐明与疾病严重程度和进展相关的细胞免疫机制,我们使用雪貂模型来模拟人类感染流感病毒后的疾病结局。有趣的是,当雪貂接种 A/Anhui/1/2013(H7N9)株时,我们观察到了不同的疾病结局。我们观察到淋巴组织中抗原呈递细胞的激活相对减少,这可能与疾病严重程度增加有关。此外,在患病动物中并未明显观察到 CD8 T 细胞耗竭。这项研究进一步深入了解了淋巴细胞在雪貂模型中对 H7N9 感染的成熟和迁移方式。