Mesh : Humans Immunity, Innate / immunology Child, Preschool Infant COVID-19 / immunology virology Child SARS-CoV-2 / immunology Female Male Nasopharynx / immunology virology microbiology Viral Load Nasal Mucosa / immunology virology microbiology Cytokines / metabolism immunology Host-Pathogen Interactions / immunology Adolescent Nose / immunology virology microbiology Coinfection / immunology virology

来  源:   DOI:10.1084/jem.20230911   PDF(Pubmed)

Abstract:
Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and bacteria in driving these responses, we performed cytokine profiling and comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts in nasopharyngeal samples from children tested for SARS-CoV-2 in 2021-22 (n = 467). Respiratory viruses and/or pathobionts were highly prevalent (82% of symptomatic and 30% asymptomatic children; 90 and 49% for children <5 years). Virus detection and load correlated with the nasal interferon response biomarker CXCL10, and the previously reported discrepancy between SARS-CoV-2 viral load and nasal interferon response was explained by viral coinfections. Bacterial pathobionts correlated with a distinct proinflammatory response with elevated IL-1β and TNF but not CXCL10. Furthermore, paired samples from healthy 1-year-olds collected 1-2 wk apart revealed frequent respiratory virus acquisition or clearance, with mucosal immunophenotype changing in parallel. These findings reveal that frequent, dynamic host-pathogen interactions drive nasal innate immune activation in children.
摘要:
COVID-19大流行期间的研究表明,与成年人相比,儿童的鼻先天免疫反应增强。为了评估鼻腔病毒和细菌在驱动这些反应中的作用,我们进行了细胞因子分析和全面,在2021-22年接受SARS-CoV-2检测的儿童鼻咽样本中,呼吸道病毒和细菌性病原体的症状无关性检测(n=467).呼吸道病毒和/或病原体非常普遍(82%的有症状儿童和30%的无症状儿童;90%和49%的<5岁儿童)。病毒检测和载量与鼻干扰素反应生物标志物CXCL10相关,先前报道的SARS-CoV-2病毒载量与鼻干扰素反应之间的差异可通过病毒共感染来解释。细菌病原体与IL-1β和TNF升高的明显促炎反应相关,但与CXCL10无关。此外,分开1-2周收集的健康1岁儿童的配对样本显示呼吸道病毒频繁获取或清除,与粘膜免疫表型平行变化。这些发现表明,动态的宿主-病原体相互作用驱动儿童鼻先天免疫激活.
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