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

TitleType I and III Interferon Productions Are Impaired in X-Linked Agammaglobulinemia Patients Toward Poliovirus but Not Influenza Virus
Authors
KeywordsDendritic cells
H1N1 influenza virus
Innate immunity
Oral poliovirus vaccine
Type I interferon
Issue Date2018
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology
Citation
Frontiers in Immunology, 2018, v. 9, p. article no. 1826 How to Cite?
AbstractBackground: X-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. Objective: To 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. Methods: Monocyte-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. Results: Upon 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. Conclusion: Production 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.
Persistent Identifierhttp://hdl.handle.net/10722/279193
ISSN
2019 Impact Factor: 5.085
2015 SCImago Journal Rankings: 2.810
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLuk, ADW-
dc.contributor.authorNI, K-
dc.contributor.authorWu, Y-
dc.contributor.authorLam, KT-
dc.contributor.authorChan, KW-
dc.contributor.authorLee, PP-
dc.contributor.authorTu, W-
dc.contributor.authorMao, H-
dc.contributor.authorLau, YL-
dc.date.accessioned2019-10-21T02:21:19Z-
dc.date.available2019-10-21T02:21:19Z-
dc.date.issued2018-
dc.identifier.citationFrontiers in Immunology, 2018, v. 9, p. article no. 1826-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/279193-
dc.description.abstractBackground: X-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. Objective: To 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. Methods: Monocyte-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. Results: Upon 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. Conclusion: Production 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.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDendritic cells-
dc.subjectH1N1 influenza virus-
dc.subjectInnate immunity-
dc.subjectOral poliovirus vaccine-
dc.subjectType I interferon-
dc.titleType I and III Interferon Productions Are Impaired in X-Linked Agammaglobulinemia Patients Toward Poliovirus but Not Influenza Virus-
dc.typeArticle-
dc.identifier.emailLam, KT: tailam@hkucc.hku.hk-
dc.identifier.emailChan, KW: kwchan@hku.hk-
dc.identifier.emailLee, PP: ppwlee@hku.hk-
dc.identifier.emailTu, W: wwtu@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.authorityLee, PP=rp00462-
dc.identifier.authorityTu, W=rp00416-
dc.identifier.authorityMao, H=rp01595-
dc.identifier.authorityLau, YL=rp00361-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2018.01826-
dc.identifier.pmid30147693-
dc.identifier.pmcidPMC6095995-
dc.identifier.scopuseid_2-s2.0-85054931599-
dc.identifier.hkuros307778-
dc.identifier.volume9-
dc.identifier.spagearticle no. 1826-
dc.identifier.epagearticle no. 1826-
dc.publisher.placeSwitzerland-

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