Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study.
Level 3 - non-randomized controlled study
Prospective cohort study with ex vivo laboratory stimulation and longitudinal clinical record review.
PubMed 34887467 · doi:10.1038/s41598-021-03044-x
What was done
Peripheral blood mononuclear cells (PBMCs) from 345 16-year-old participants in a population-based birth cohort were stimulated ex vivo with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A). The authors measured sex differences in interferon (IFN-alpha, IFN-beta, IFN-gamma) and chemokine responses, and examined healthcare records for infant respiratory hospitalizations.
What was found
IFN-alpha responses to all tested viruses and stimuli were 1.34- to 2.06-fold lower in males than females (P = 0.018 to P < 0.001). IFN-beta, IFN-gamma, and IFN-induced chemokines were also lower in males across all stimuli. Healthcare records showed that 12.1% of males and 6.6% of females had been hospitalized with respiratory infections in infancy (P = 0.017).
Why it matters
This study provides an innate immune mechanism—reduced systemic interferon production—that may explain observed sex disparities in morbidity and hospitalizations from respiratory viral infections.
Limits
Innate immune responses were assessed at age 16 rather than during infancy when the recorded hospitalizations took place. The study assayed peripheral blood mononuclear cells rather than airway mucosal tissue, and the abstract lacks absolute cytokine levels and adjustment for potential clinical confounders.
Cited by
- contradicts The systemic inflammatory response to a common cold is greater in men than in women.