FILAGGRIN AND CYTOKINES IN RESPIRATORY SAMPLES OF PRETERM INFANTS AT
VIRAL RESPIRATORY INFECTION RISK
Abstract
Background: Respiratory viral infections (RVIs) are frequent in preterm
infants and may have long-term impact on respiratory morbidity,
especially those with bronchopulmonary dysplasia (BDP). The immune
response and respiratory are key defence elements, so the purpose of
this study is to evaluate the immune response regulation and the
respiratory epithelial barrier integrity in the preterm infants
suffering RVIs during Neonatal Intensive Care Unit (NICU) admission.
Materials and methods: Nasopharyngeal aspirate (NPA) was obtained,
separating cells from supernatants. Viral detection was performed by
RT-nested PCR, and gene expression by qPCR. Proteins were detected by
western blot and ELISA or Luminex. Small airway epithelial cells (SAEC)
were stimulated with Poly:IC and/or wounds. Results: Pre-infection
samples from 26 preterm infants that later developed RVIs had less
frequency of filaggrin gene expression and fewer protein levels compared
to 23 noninfected controls. Conversely, filaggrin, IL-1β, MIP-1β, VEGF
and HIF-1α levels were higher in pre-infection supernatant samples,
being infection-risk biomarkers. IL-17A, RANTES, VEGF, and HIF-1α levels
were higher during and post infection, while MCP-1 and amphiregulin were
reduced after infection. Small airway epithelial cells (SAEC) stimulated
by poly:IC reduced filaggrin gene expression and increased its levels at
supernatant. Finally, poly:IC stimulation over SAEC increased TLR3 and
TSLP expression, while reduced AREG. Conclusion: Filaggrin gene
expression and protein quantity was reduced at cellular level of the
NPA, while its secreted levels were increased in basal samples from
infected newborns and in SAEC stimulated with poly:IC. Our findings
highlight the importance of filaggrin as a factor facilitating RVIs.