Host-microbial interactions at the nasal mucosa in young children and adults

Respiratory tract infections are an important global cause of morbidity and mortality. Young children are at increased risk for these infections and are frequently colonised with pathogens that can cause such infections. However, how the mucosal immune system differs between children and adults is still relatively unknown. Here, we collected nasal samples from 50 young children and 318 young adults to study how the mucosal immune system and host-microbe interactions differ with age. We used multi-omics data integration techniques to combine host (immunophenotyping, transcriptomic and cytokines) and microbial (16S-rRNA sequencing, viral PCRs and pneumococcal culture) datasets. The mucosa of young children had a paucity of granulocytes, while B cells and CD8+ and CD8-CD4- T cell subsets were increased relative to adults. The nasal mucosa of children also showed higher levels of immune activation and inflammation than those of adults, which associated with the presence of Haemophilus spp. and pneumococcus. In adults, Haemophilus spp. presence was associated with T cell and monocyte recruitment. Pneumococcal colonization in children was also linked to T cells activation, in particular CD8+ T cells. In contrast, colonization with commensals Corynebacterium and Dolosigranulum was associated with reduced T cell activation and gene modules of nasal γδ T cells in children. In adults, a correlation between neutrophil degranulation and Dolosigranulum abundance was observed. Thus, young children demonstrate alterations in the nasal immune compartment compared to adults. Moreover, nasal immune responses in relationship to microbial pathogens differed between children and adults.

Keywords