Nasal cathelicidin is expressed in early life and is increased during mild, but not severe respiratory syncytial virus infection

TL;DR

Nasal cathelicidin levels in infants increase with age and are higher during mild RSV infections, but not during severe cases, suggesting a role in immune defense.

Contribution

The study reveals how nasal cathelicidin expression changes in early life and its differential response to mild versus severe RSV infection.

Findings

Nasal cathelicidin levels are low at birth but increase by 9 months, reaching adult levels.

Cathelicidin levels are elevated in infants with mild RSV but not in those with severe RSV.

Nasal cathelicidin is associated with inflammation and microbial community composition in the upper airway.

Abstract

Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown. Infant cohorts were analysed to characterise early life nasal cathelicidin levels, revealing low expression levels in the first week of life, with increased levels at 9 months which are comparable to 2-year-olds and healthy adults. No impact of prematurity on nasal cathelicidin expression was observed, nor were there effects of sex or birth mode, however, nasal cathelicidin expression was lower in the first week-of-life in winter births. Nasal cathelicidin levels were positively associated with specific inflammatory markers and demonstrated to be associated with microbial community composition. Importantly, levels of nasal cathelicidin expression were elevated in infants with mild RSV infection, but, in contrast, were not upregulated in infants hospitalised with severe RSV infection. These data suggest important relationships between nasal cathelicidin, upper airway microbiota, inflammation, and immunity against RSV infection, with interventional potential.

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