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