Gautam Avishekh, Akauliya Madhav, Thapa Bikash, Park Byoung Kwon, Kim Dongbum, Kim Jinsoo, Lee Keunwook, Choi Kyung Chan, Bae Joon-Yong, Park Man-Seong, Lee Younghee, Kwon Hyung-Joo
Department of Microbiology, College of Medicine, Hallym University, Chuncheon, South Korea.
Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea.
Front Microbiol. 2020 Jul 17;11:1713. doi: 10.3389/fmicb.2020.01713. eCollection 2020.
In humans, respiratory infections with influenza A viruses can be lethal, but it is unclear whether non-respiratory influenza A infections can be equally lethal. Intraperitoneal infection makes the abdominal and pelvic organs accessible to pathogens because of the circulation of peritoneal fluid throughout the pelvis and abdomen. We found that high-dose intraperitoneal infection in mice with influenza A viruses resulted in severe sclerosis and structural damage in the pancreas, disruption of ovarian follicles, and massive infiltration of immune cells in the uterus. The intraperitoneal infections also caused robust upregulation of proinflammatory mediators including IL-6, BLC, and MIG. In addition, low-dose intraperitoneal infection with one influenza strain provided cross-protection against subsequent intraperitoneal or intranasal challenge with another influenza strain. Our results suggest that low-dose, non-respiratory administration might provide a route for influenza vaccination. Furthermore, these results provide insight on the pathological role of influenza A viruses in high-risk patients, including women and diabetic individuals.
在人类中，甲型流感病毒引起的呼吸道感染可能是致命的，但尚不清楚非呼吸道甲型流感感染是否同样具有致命性。由于腹膜液在整个盆腔和腹部循环，腹腔感染使病原体能够接触到腹部和盆腔器官。我们发现，用甲型流感病毒对小鼠进行高剂量腹腔感染会导致胰腺严重硬化和结构损伤、卵巢卵泡破坏以及子宫内免疫细胞大量浸润。腹腔感染还会导致促炎介质（包括白细胞介素-6、B淋巴细胞趋化因子和巨噬细胞炎症蛋白-1γ）的强烈上调。此外，用一种流感毒株进行低剂量腹腔感染可为后续用另一种流感毒株进行腹腔或鼻内攻击提供交叉保护。我们的结果表明，低剂量非呼吸道给药可能为流感疫苗接种提供一条途径。此外，这些结果为甲型流感病毒在高危患者（包括女性和糖尿病患者）中的病理作用提供了见解。
