RSV Promotes Epithelial Neuroendocrine Phenotype Differentiation through NODAL Signaling Pathway

et al. 2023

Preprint

Background: The lung-brain-axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggest that pulmonary viral infections can lead to distinct pathological imprints in the brain, thereby the need to explore and understand this mechanism and find possible interventions. Objective: This study used RSV infection in mice as a model to establish the potential lung-brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, thereby compromising the immune barriers and thus induces significant shift in microglia phenotype. Methods: Mice were randomized into the Control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Ampicillin was given intratracheal instillation and seven days after the respective treatments, the mice were anesthetized. Hematoxylin-eosin (HE) staining of lung tissue to detect histopathology. Immunofluorescence label of specific target antigens in both the lung and brain tissues, namely, Malondialdehyde (MDA) and Superoxide dismutase (SOD) were used as markers of cellular damage. RT-qPCR was used to detect viral RNA in both tissues, ELISA to measure IL-1β, iNOS, IL-10 and Arg1 in the supernatant and 16s DNA technology were used to detect the lung microflora. Results: We found out that RSV infection induces elevated oxidative stress, reduced anti-oxidant and caused significant dysbacteriosis in the lungs of the mice. Pulmonary microbes were found affecting Th1-type immunoreactivity induced by RSV infection and eventually, microbiota in lung induced microglia phenotype shift in the brain of the mice. Conclusion. This study was able to establish that RSV infection can disrupt the pulmonary microbiome and immune barriers to induce microglia phenotype shift. Thus, we recommend a large sample size study with robust data analysis for the long-term effects of antibiotics and RSV infection on brain physiology.

Section: Introductionmentioning

confidence: 99%

Respiratory syncytial virus infection disrupts pulmonary microbiota and immune barriers to induce microglia phenotype shift

Tan

et al. 2023

Preprint

“…3 There is considerable evidence that a significant proportion of children hospitalized with RSV bronchiolitis suffer recurrent wheezing and even asthma in the months and years following recovery, much more frequently than non-RSV infected individuals. 4,5 The homeostasis of the respiratory microbiome is closely related to the immune defense function of the respiratory system. It has been found that microbial signaling is necessary to supplement and activate anti-inflammatory and regulatory T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

“…Respiratory syncytial virus (RSV) has also been shown to be associated with asthma, myocarditis, and other diseases in the elderly and immunocompromised patients 3 . There is considerable evidence that a significant proportion of children hospitalized with RSV bronchiolitis suffer recurrent wheezing and even asthma in the months and years following recovery, much more frequently than non‐RSV infected individuals 4,5 …”

Section: Introductionmentioning

confidence: 99%

Respiratory syncytial virus infection disrupts pulmonary microbiota to induce microglia phenotype shift

Journal of Medical Virology

Mao

et al. 2023

Self Cite

The lung−brain axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggests that pulmonary viral infections can lead to distinct pathological imprints in the brain, so there is a need to explore and understand this mechanism and find possible interventions. This study used respiratory syncytial virus (RSV) infection in mice as a model to establish the potential lung−brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, compromise immune barriers, and induce a significant shift in microglia phenotype. One week old mice were randomized into the control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Seven days after the respective treatments, the mice were anaesthetized. Immunofluorescence and real‐time qRT‐PCR was used to detect virus. Hematoxylin‐eosin staining was used to detect histopathology. Malondialdehyde and superoxide dismutase were used to determine oxidative stress and antioxidant capacity. Real‐time qRT‐PCR and enzyme‐linked immunosorbent assay (ELISA) were used to measure Th differentiation in the lung. Real‐time qRT‐PCR, ELISA, and confocal immunofluorescence were used to determine the microglia phenotype. 16S DNA technology was used to detect lung microflora. RSV infection induces elevated oxidative stress, reduced antioxidant, and significant dysbacteriosis in the lungs of mice. Pulmonary microbes were found to enhance Th1‐type immunoreactivity induced by RSV infection and eventually induced M1‐type dominant microglia in the brains of mice. This study was able to establish a correlation between the pulmonary microbiome and brain function. Therefore, we recommend a large sample size study with robust data analysis for the long‐term effects of antibiotics and RSV infection on brain physiology.

miR-34b/c-5p/CXCL10 Axis Induced by RSV Infection Mediates a Mechanism of Airway Hyperresponsive Diseases

Liú

et al. 2023

Biology

Background: RSV is closely correlated with post-infection airway hyperresponsive diseases (AHD), but the mechanism remains unclear. Objective: Due to the pivotal role of miRNAs in AHD, we analyzed the differentially expressed miRNAs (DEmiRs) in RSV-infected patients, asthma patients, and COPD patients from public datasets and explored the mechanisms of association between RSV and AHD. Methods: We obtained miRNA and mRNA databases of patients with RSV infection, as well as miRNA databases of asthma and COPD patients from the GEO database. Through integrated analysis, we screened DEmiRs and DEGs. Further analysis was carried out to obtain the hub genes through the analysis of biological pathways and enrichment pathways of DEGs targeted by DEmiRs and the construction of a protein-protein interaction (PPI) network. Results: The five differential molecules (miR-34b/c-5p, Cd14, Cxcl10, and Rhoh) were verified through in vivo experiments that had the same expression trend in the acute and chronic phases of RSV infection. Following infection of BEAS-2B cells with RSV, we confirmed that RSV infection down-regulated miR-34b/c-5p, and up-regulated the expression levels of CXCL10 and CD14. Furthermore, the results of the dual-luciferase reporter assay showed that CXCL10 was the target of hsa-miR-34c-5p. Conclusions: miR-34b/c-5p/CXCL10 axis mediates a mechanism of AHD.