Koch Rebecca M, Kox Matthijs, van den Kieboom Corné, Ferwerda Gerben, Gerretsen Jelle, Ten Bruggencate Sandra, van der Hoeven Johannes G, de Jonge Marien I, Pickkers Peter
Radboudumc, HB, Radboud Institute for Molecular Life Sciences, Department of Intensive Care Medicine, HB, Nijmegen, The Netherlands.
Radboud center for Infectious Diseases (RCI), HB, Nijmegen, The Netherlands.
PLoS One. 2018 Feb 15;13(2):e0191937. doi: 10.1371/journal.pone.0191937. eCollection 2018.
Naturally, development of adaptive immunity following HRV infection affects the immune response. However, it is currently unclear whether or not HRV re-exposure within a short time frame leads to an altered innate immune response. The "experimental cold model" is used to investigate the pathogenesis of HRV infection and allows us to investigate the effects of repeated exposure on both local and systemic innate immunity.
40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. One week later, all subjects received HRV-16. Baseline seronegative subjects (n = 18) were included for further analysis.
Infection rate was 82%. Primary HRV infection induced a marked increase in viral load and IP-10 levels in nasal wash, while a similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10 plasma levels, HRV infection did not induce systemic immune effects nor lower respiratory tract inflammation. With similar viral load present during the second HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually declined, with a similar trend for IL-10.
Upon a second HRV challenge one week after the first, a less pronounced response for several innate immune parameters is observed. This could be the result of immunological tolerance and possibly increases vulnerability towards secondary infections.
自然情况下,人 rhinovirus(HRV)感染后适应性免疫的发展会影响免疫反应。然而,目前尚不清楚在短时间内再次接触 HRV 是否会导致先天性免疫反应改变。“实验性感冒模型”用于研究 HRV 感染的发病机制,并使我们能够研究重复接触对局部和全身先天性免疫的影响。
40 名健康男女(1:1)受试者经鼻腔接种 HRV-16 或安慰剂。一周后,所有受试者均接受 HRV-16 接种。纳入基线血清阴性受试者(n = 18)进行进一步分析。
感染率为 82%。初次 HRV 感染导致鼻腔灌洗液中病毒载量和 IP-10 水平显著升高,IL-6 和 IL-10 也呈现类似趋势。除血浆中 IP-10 水平升高外,HRV 感染未诱导全身免疫效应或下呼吸道炎症。在第二次 HRV 攻击期间,鼻腔灌洗液中 IP-10 和 IL-6 虽病毒载量相似但未升高,而是逐渐下降,IL-10 也呈类似趋势。
在首次感染一周后再次接受 HRV 攻击时,观察到几种先天性免疫参数的反应不那么明显。这可能是免疫耐受的结果,并且可能增加对继发性感染的易感性。