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

Abstract

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.

Infectious viruses and neurodegenerative diseases: The mitochondrial defect hypothesis

“…Substantial research affirms the correlation between respiratory viruses and neurodegenerative diseases. 69,70 For example, an epidemiological study found a link between influenza A virus (IAV) infection and PD onset years later, with IAV detected in the substantia nigra of PD patients. Animal models showed that H1N1 infection induced sustained microglia activation, suggesting chronic inflammation could contribute to neurodegeneration.…”

“…Drugs targeting microtubule stability, kinesin motors, or suppressing mitochondrial ROS production effectively inhibit RSV production, as shown in a mouse model where they also alleviated virus-induced lung inflammation. 70,86 A preliminary study using a knockout (KO) cell line deficient in mitochondrial complex I activity suggested that host cell mitochondria are crucial targets for RSV. Specifically, mitochondrial complex I modulates respiration and increases mtROS levels, contributing to RSV infection.…”