Distinct airway epithelial immune responses after infection with SARS-CoV-2 compared to H1N1

Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5-5.6 years old) and adult (n = 4; 47-63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.

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Helen Stölting, Laury Baillon, Rebecca Frise, Katie Bonner, Richard J Hewitt, Philip L Molyneaux, Mindy L Gore; Breathing Together Consortium; Wendy S Barclay, Sejal Saglani #, Clare M Lloyd #

期刊 Mucosal Immunol
影响因子 8
起止号 2022 May;15(5):952-963.
种属 Human
技术平台抗体芯片
应用领域呼吸系统
研究方向呼吸系统
细胞类型上皮细胞
疾病类型新冠
检测蛋白 Adiponectin/Acrp30,IFN-gamma,CCL2/MCP-1,Angiogenin,IGFBP-2,CCL7/MCP-3,Angiopoietin-1,IGFBP-3,M-CSF,Angiopoietin-2,IL-1 alpha/IL-1F1,MIF,Apolipoprotein A1,IL-1 beta/IL-1F2,CXCL9/MIG,BAFF/BLyS/TNFSF13B,IL-1ra/IL-1F3,CCL3/CCL4 MIP-1 alpha/beta,BDNF,IL-2,CCL20/MIP-3 alpha,CD14,IL-3,CCL19/MIP-3 beta,CD30,IL-4,MMP-9,CD31/PECAM-1,IL-5,Myeloperoxidase,CD40 Ligand/TNFSF5,IL-6,Osteopontin (OPN),Chitinase 3-like,IL-8,PDGF-AA,Complement Component C5/C5a,IL-10,PDGF-AB/BB,Complement Factor D,IL-11,Pentraxin 3/TSF-14,C-Reactive Protein/CRP,IL-12 p70,CXCL4/PF4,Cripto-1,IL-13,RAGE,Cystatin C,IL-15,CCL5/RANTES,Dkk-1,IL-16,RBP4,DPPIV/CD26,IL-17A,Relaxin-2,EGF,IL-18 BPa,Resistin,CXCL5/ENA-78,IL-19,CXCL12/SDF-1 alpha,Endoglin/CD105,IL-22,Serpin E1/PAI-1,EMMPRIN,IL-23,SHBG,Fas Ligand,IL-24,ST2/IL1 R4,FGF basic,IL-27,CCL17/TARC,KGF/FGF-7,IL-31,TFF3,FGF-19,IL-32 alpha/beta/gamma,TfR,Flt-3 Ligand,IL-33,TGF-alpha,G-CSF,IL-34,Thrombospondin-1,GDF-15,CXCL10/IP-10,TIM-1,GM-CSF,CXCL11/I-TAC,TNF-alpha,CXCL1/GRO alpha,Kallikrein 3/PSA,uPAR,Growth Hormone (GH),Leptin,VCAM-1,HGF,LIF,VEGF,ICAM-1/CD54,Lipocalin-2/NGAL,Vitamin D BP

Abstract

Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5-5.6 years old) and adult (n = 4; 47-63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.

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Abstract