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.

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

“…We also showed that Nrf2 may be involved in altering the phenotype of ES –induced macrophages. Our results are in agreement with a recent study suggesting that T. spiralis infection can mitigate inflammation by upregulating Nrf2 expression ( 16 ). We found that ES -treated Nrf2 KO macrophages expressed less IL-10, which is essential for the anti- inflammatory effect ( 23 ) and a higher level of IL-12 which can promote a Th1 response ( 39 ).…”

“…It has been reported that activation of Nrf2 leads to M2 macrophage polarization ( 14 , 15 ). Recent study have demonstrated that upregulated Nrf2 expression contributes to immnunomudulatory role of T. spiralis infection in host ( 16 ), however, details related to the mechanism is still unknown.…”

Preexisting Trichinella spiralis infection attenuates the severity of Pseudomonas aeruginosa-induced pneumonia

“…Evidence also indicates that T . spiralis infection has attenuated influenza or respiratory syncytial virus -associated pathologies in mice [ 17 , 24 ]. Yet, not a single study has reported the effect of T .…”

“…Multiple studies have confirmed the anti-inflammatory effect of T . spiralis in animal models, such as allergies, autoimmune disease, rheumatoid arthritis and viral pulmonary inflammation [ 16 , 17 ]. Here, we investigated the role of T .…”

Influenza Virus-like Particle (VLP) Vaccines Expressing the SARS-CoV-2 S Glycoprotein, S1, or S2 Domains

“…S1 and S2 antigens were purchased from Sino Biological (Beijing, China). Antigen-specific antibody responses were determined using ELISA, as described previously [ 24 ]. Briefly, 96-well plates were coated using identical concentrations of S1 and S2 antigens (both 1 μg/mL) combined in carbonate coating buffer overnight at 4 °C.…”