Abstract
Respiratory syncytial virus (RSV) infection affects the lives of neonates throughout the globe, causing a high rate of mortality upon hospital admission. Yet, therapeutic options to deal with this pulmonary pathogen are currently limited. Helminth therapy has been well received for its immunomodulatory role in hosts, which are crucial for mitigating a multitude of diseases. Therefore, in this study, we used the helminth Trichinella spiralis and assessed its capabilities for modulating RSV infection as well as the inflammatory response induced by it in mice. Our results revealed that RSV-specific antibody responses were enhanced by pre-existing T. spiralis infection, which also limited pulmonary viral replication. Diminished lung inflammation, indicated by reduced pro-inflammatory cytokines and inflammatory cell influx was confirmed, as well as through histopathological assessment. We observed that inflammation-associated nuclear factor kappa-light-chain enhancement of activated B cells (NF-κB) and its phosphorylated forms were down-regulated, whereas antioxidant-associated nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression was upregulated in mice co-infected with T. spiralis and RSV. Upregulated Nrf2 expression contributed to increased antioxidant enzyme expression, particularly NQO1 which relieved the host of oxidative stress-induced pulmonary inflammation caused by RSV infection. These findings indicate that T. spiralis can mitigate RSV-induced inflammation by upregulating the expression of antioxidant enzymes.
Highlights
Respiratory syncytial virus (RSV) infection is a common cause of neonatal and infantile acute lower respiratory infection (ALRI) [1,2]
These findings indicate that T. spiralis infection control (Ts). spiralis can mitigate RSV-induced inflammation by upregulating the expression of antioxidant enzymes
Cells 2020, 9, 1314 relationship between ROS production and pulmonary inflammation has been established through previous studies, as pulmonary inflammation and the lung pathologies associated with RSV infection were attenuated through antioxidant treatment [7]
Summary
Respiratory syncytial virus (RSV) infection is a common cause of neonatal and infantile acute lower respiratory infection (ALRI) [1,2]. Cells 2020, 9, 1314 relationship between ROS production and pulmonary inflammation has been established through previous studies, as pulmonary inflammation and the lung pathologies associated with RSV infection were attenuated through antioxidant treatment [7]. To this extent, a therapeutic option that regulates oxidative stress to maintain homeostasis would have a significant impact on RSV infection control. Not a single study has reported the effect of T. spiralis infection in regulating RSV-induced inflammation in the lungs. Our results indicate that infection with T. spiralis ameliorates the inflammatory response in mice by upregulating the expression of antioxidant enzymes, which are down-regulated by RSV. The findings of the current study further contribute to the previous works and suggest that T. spiralis can regulate oxidative stress in hosts as a mechanism of immunomodulation
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