Filaggrin and cytokines in respiratory samples of preterm infants at risk for respiratory viral infection

Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU. ; This study has been partially supported by ISCIII – Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) grants FI19/00067, PI18/00167, PI21/00896, PI18CIII/00009 and FEDER funds (Fondo Europeo de Desarrollo Regional); Sociedad Española de Alergología e Inmunología Clínica (SEAIC)Beca19A04_Valverde; Alfonso X El Sabio University Grant: VIII Convocatoria Santander-UAX; CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health Initiative. ; Sí