Background: From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses, shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort. Methods: Peripheral blood mononuclear cells from 51 children (32 asthmatics, 19 healthy controls), participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analyzed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high troughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis. Results: High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile, however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed amongst immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations. Conclusions: Antiviral cytokines responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not affected by TLR-induced immune responses.

Background: The impact of physical activity (PA) on immune response is a hot topic in exercise immunology, but studies involving asthmatic children are scarce. We examine the level of PA and TV attendance (TVA) in asthmatic children to assess the role on asthma control and immune response to various stimulants. Methods: Weekly PA and daily TVA were obtained from questionnaires at inclusion of the PreDicta study. PBMC cultures were stimulated with phytohemagglutinin (PHA), R848, poly I:C and zymosan. Cytokines were measured and quantified in cell culture supernatants using luminometric multiplex immunofluorescence beads-based assay. Results: Asthmatic preschoolers showed significantly more TVA than their healthy peers (58.6% vs. 41.5% 1-3h daily and only 25.7% vs. 47.2% ≤ 1h daily). Poor asthma control was associated with less frequent PA (75% no or occasional activity in uncontrolled vs. 20% in controlled asthma; 25% ≥ 3x weekly vs. 62%). Asthmatics with increased PA exhibited elevated cytokine levels in response to stimulants, suggesting a readiness of circulating immune cells for type-1, -2 and -17 cytokine release compared to low-PA and high-TVA subjects. Low PA and high TVA were associated with increased proinflammatory cytokines. Proinflammatory cytokines were correlating with each other in in-vitro immune responses of asthmatic children, but not healthy controls. Conclusion: Asthmatic children show more sedentary behavior than healthy subjects, while poor asthma control leads to a decrease in PA. Asthmatic children profit from exercise, as elevated cytokine levels in stimulated conditions indicate an immune system prepared for a strong response in case of infection.