Abstract
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.
Highlights
Respiratory influenza infections account for about 290,000–650,000 deaths worldwide each year1
We found that the mice developed severe virus infection in the abdominal and pelvic organs, leading to organ failure and greatly increased expression of chemokines and cytokines in the pancreas, ovary, and uterus
The levels of influenza H3N2-reactive IgG and IgM increased in the peritoneal cavity fluids and sera in a dose-dependent manner (Figures 1A–D), the number of B cells in the peritoneal cavity and bone marrow decreased after infection with the highest dose (1 × 108 pfu) of the virus (Gautam et al, 2019)
Summary
Respiratory influenza infections account for about 290,000–650,000 deaths worldwide each year. Studies of the pathogenesis of influenza A viruses predominantly focus on the respiratory tract and related organs (Kuiken and Taubenberger, 2008; Taubenberger and Morens, 2008; Guarner and Falcon-Escobedo, 2009). Influenza infections of the respiratory tract can lead to involvement of other organs, such as encephalitis and pericarditis (Edelen et al, 1974; Delorme and Middleton, 1979; Protheroe and Mellor, 1991; McCullers et al, 1999; Tamaki et al, 2009). Highly pathogenic avian influenza viruses were reported to replicate in multiple organs of birds including the respiratory and gastrointestinal tracks (Kwon et al, 2017; Prokopyeva et al, 2019)
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