Introduction: Infants are hyper-susceptible to the inflammatory effects of respiratory viral insults, and resultant acute viral bronchiolitis (AVB) leads to hospitalisation more frequently relative to older children, for reasons unknown.
Objectives: To characterise the cellular and molecular mechanisms underlying infant AVB.
Methods: Comparative cellular and molecular (RNA-Seq) profiling was employed on paired PBMC obtained from infants (0-18 months, n=15) and young children (1.5-5 years of age, n=16) presenting to Emergency at Child Health Research Centre (Queensland), during an AVB event and following recovery. Viral infection was confirmed by RT-qPCR in saline nasal washes.
Results: Viral prevalence was HRV 50% and RSV 50% in infants. In children, it was HRV 43.8%, RSV 12.5% and influenza 18.8%. Total numbers of inflammatory cells were decreased during the acute visit compared to recovery, including CD4+Tcells (p=0.001) and CD8+Tcells (p=0.005) in children (no change in infants), Tregs in both age groups (p=0.042), Bcells (p=0.025) in infants, pDCs (p<0.002) and cDC(CD123-) (p<0.004) in both age groups, and cDC(cDC123-) (p=0.001) in children. In contrast, monocytes were increased at the acute visit (p=0.049) in infants. The acute PBMC transcriptome in infants displayed a perturbation of 4,335 genes versus 6,677 in children. Pathways analysis of the upregulated genes in the infants identified enrichment for innate immune activation/cytokine signalling (p=1.2x10-15), type I interferon signalling (p=8.7x10-12) and antiviral response mechanisms (p=1.2x10-5). In contrast, responses in older children were dominated by antibody-mediated complement (p=2.4x10-7) and FCGR activation (p=4.4x10-6) with classical innate immune pathways attenuated relative to the infants.
Conclusion: Severe AVB during infancy may be associated with hyperactivation and/or dysregulation of type 1 interferon mechanisms. Ongoing analyses are seeking to define upstream regulators driving these and related pathways in the two age groups.