Type I and III Interferon Productions Are Impaired in X-Linked Agammaglobulinemia Patients Toward Poliovirus but Not Influenza Virus

Frontiers in Immunology

Koon-Wing Chan¹  Yuet Wu¹  Kwok-Tai Lam¹  Anderson Dik Wai Luk¹  Huawei Mao²  Ke Ni³  Wenwei Tu⁴  Pamela P. Lee⁴  Yu Lung Lau⁴ 

[1] Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong;Department of Rheumatology and Immunology, Ministry of Education Key Laboratory of Child Development and Disorder, Children’s Hospital of Chongqing Medical University, Chongqing, China;Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China;Shenzhen Primary Immunodeficiency Diagnostic and Therapeutic Laboratory, Department of Paediatrics, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China;

关键词: type I interferon;    type III interferon;    X-linked agammaglobulinemia;    oral poliovirus vaccine;    H1N1 influenza virus;    innate immunity;   

DOI  :  10.3389/fimmu.2018.01826

来源: DOAJ

【 摘 要 】

BackgroundX-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by Bruton’s tyrosine kinase (BTK) mutation. Patients are susceptible to severe enterovirus infections. The underlying mechanism remains unknown. BTK is involved in toll-like receptors pathway, which initiates antiviral responses including interferon (IFN) productions.ObjectiveTo demonstrate type I and III IFN productions in dendritic cells of XLA patients is decreased in response to oral poliovirus vaccine (OPV) but not H1N1 virus.MethodsMonocyte-derived dendritic cells (MoDCs) were derived from nine XLA patients aged 22–32 years old and 23 buffy coats from Hong Kong Red Cross blood donors. LFM-A13 was used to inhibit BTK. OPV Sabin type 1 and H1N1 influenza virus were used to stimulate MoDCs with RPMI as mock stimulation. The antiviral cytokine productions and phenotypic maturation of MoDCs were determined 24 h post-stimulation. OPV RNA was determined at 0, 6, 12, and 24 h post-stimulation.ResultsUpon OPV stimulation, IFN-α2, IFN-β, and IFN-λ1 productions in MoDCs from XLA patients and BTK-inhibited MoDCs of healthy controls were significantly lower than that from healthy controls. Whereas upon H1N1 stimulation, the IFN-α2, IFN-β, and IFN-λ1 productions were similar in MoDCs from XLA patients, BTK-inhibited MoDCs of healthy controls and healthy controls. The mean fluorescent intensities (MFI) of CD83, CD86, and MHC-II in MoDCs from XLA patients in response to OPV was similar to that in response to mock stimulation, while the MFI of CD83, CD86, and MHC-II were significantly higher in response to H1N1 stimulation than that in response to mock stimulation. Whereas, the MFI of CD83, CD86, and MHC-II in MoDCs of healthy controls were significantly higher in response to both OPV and H1N1 stimulation compared to that in response to mock stimulation.ConclusionProduction of type I and III IFN in response to OPV was deficient in MoDCs from XLA patients, but was normal in response to H1N1 due to deficient BTK function. Moreover, phenotypic maturation of MoDCs from XLA patients was impaired in response to OPV but not to H1N1. These selective impairments may account for the unique susceptibility of XLA patients toward severe enterovirus infections.

【 授权许可】

Unknown