Abstract：
The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34-2.06-fold lower in males than females (P = 0.018 - < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.
摘要：
解释男性呼吸道感染发病率和死亡率过高的机制知之甚少。先天性免疫应答在防止呼吸道病毒感染中至关重要。我们假设男性可能缺乏对呼吸道病毒的先天免疫反应。我们用三种活的呼吸道病毒（鼻病毒A16和A1，以及呼吸道合胞病毒）和两种病毒模拟物（R848和CpG-A，在基于人群的出生队列中刺激了345名16岁参与者的外周血单核细胞。模拟对SARS-CoV-2的反应）并研究干扰素（IFN）反应的性别差异。男性对所有病毒和刺激的IFN-α反应比女性低1.34-2.06倍（P=0.018-<0.001）。IFN-β,在所有刺激/病毒中,IFN-γ和IFN诱导的趋化因子在雄性中也是缺乏的。医疗记录显示，12.1%的男性和6.6%的女性在婴儿期因呼吸道感染住院（P=0.017）。总之,男性先天抗病毒免疫受损可能导致男性呼吸道病毒感染的高发病率和死亡率.
