Preliminary Trichinella spiralis Infection Ameliorates Subsequent RSV Infection-Induced Inflammatory Response

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.