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Article: Reduced type I interferon production by dendritic cells and weakened antiviral immunity in patients with Wiskott-Aldrich syndrome protein deficiency

TitleReduced type I interferon production by dendritic cells and weakened antiviral immunity in patients with Wiskott-Aldrich syndrome protein deficiency
Authors
Keywordsvirus
CD8 T cells
Type I interferon
Wiskott-Aldrich syndrome protein
Wiskott-Aldrich syndrome
diabetes
dendritic cells
Issue Date2013
Citation
Journal of Allergy and Clinical Immunology, 2013, v. 131, n. 3, p. 815-824.e2 How to Cite?
AbstractBackground: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by absence of Wiskott-Aldrich syndrome protein (WASP) expression, resulting in defective function of many immune cell lineages and susceptibility to severe bacterial, viral, and fungal infections. Despite a significant proportion of patients with WAS having recurrent viral infections, surprisingly little is known about the effects of WASP deficiency on antiviral immunity. Objective: We sought to evaluate the antiviral immune response in patients with WASP deficiency in vivo. Methods: Viral clearance and associated immunopathology were measured after infection of WASP-deficient (WAS KO) mice with lymphocytic choriomeningitis virus (LCMV). Induction of antiviral CD8 + T-cell immunity and cytotoxicity was documented in WAS KO mice by means of temporal enumeration of total and antigen-specific T-cell numbers. Type I interferon (IFN-I) production was measured in serum in response to LCMV challenge and characterized in vivo by using IFN-I reporter mice crossed with WAS KO mice. Results: WAS KO mice showed reduced viral clearance and enhanced immunopathology during LCMV infection. This was attributed to both an intrinsic CD8+ T-cell defect and defective priming of CD8+ T cells by dendritic cells (DCs). IFN-I production by WAS KO DCs was reduced both in vivo and in vitro. Conclusions: These studies use a well-characterized model of persistence-prone viral infection to reveal a critical deficiency of CD8 + T-cell responses in murine WASP deficiency, in which abrogated production of IFN-I by DCs might play an important contributory role. These findings might help us to understand the immunodeficiency of WAS. © 2012 American Academy of Allergy, Asthma & Immunology.
Persistent Identifierhttp://hdl.handle.net/10722/292052
ISSN
2023 Impact Factor: 11.4
2023 SCImago Journal Rankings: 3.701
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLang, Philipp A.-
dc.contributor.authorShaabani, Namir-
dc.contributor.authorBorkens, Stephanie-
dc.contributor.authorHonke, Nadine-
dc.contributor.authorScheu, Stefanie-
dc.contributor.authorBooth, Sarah-
dc.contributor.authorBrenner, Dirk-
dc.contributor.authorMeryk, Andreas-
dc.contributor.authorBarthuber, Carmen-
dc.contributor.authorRecher, Mike-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorOhashi, Pamela S.-
dc.contributor.authorHäussinger, Dieter-
dc.contributor.authorGriffiths, Gillian M.-
dc.contributor.authorThrasher, Adrian J.-
dc.contributor.authorBouma, Gerben-
dc.contributor.authorLang, Karl S.-
dc.date.accessioned2020-11-17T14:55:40Z-
dc.date.available2020-11-17T14:55:40Z-
dc.date.issued2013-
dc.identifier.citationJournal of Allergy and Clinical Immunology, 2013, v. 131, n. 3, p. 815-824.e2-
dc.identifier.issn0091-6749-
dc.identifier.urihttp://hdl.handle.net/10722/292052-
dc.description.abstractBackground: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by absence of Wiskott-Aldrich syndrome protein (WASP) expression, resulting in defective function of many immune cell lineages and susceptibility to severe bacterial, viral, and fungal infections. Despite a significant proportion of patients with WAS having recurrent viral infections, surprisingly little is known about the effects of WASP deficiency on antiviral immunity. Objective: We sought to evaluate the antiviral immune response in patients with WASP deficiency in vivo. Methods: Viral clearance and associated immunopathology were measured after infection of WASP-deficient (WAS KO) mice with lymphocytic choriomeningitis virus (LCMV). Induction of antiviral CD8 + T-cell immunity and cytotoxicity was documented in WAS KO mice by means of temporal enumeration of total and antigen-specific T-cell numbers. Type I interferon (IFN-I) production was measured in serum in response to LCMV challenge and characterized in vivo by using IFN-I reporter mice crossed with WAS KO mice. Results: WAS KO mice showed reduced viral clearance and enhanced immunopathology during LCMV infection. This was attributed to both an intrinsic CD8+ T-cell defect and defective priming of CD8+ T cells by dendritic cells (DCs). IFN-I production by WAS KO DCs was reduced both in vivo and in vitro. Conclusions: These studies use a well-characterized model of persistence-prone viral infection to reveal a critical deficiency of CD8 + T-cell responses in murine WASP deficiency, in which abrogated production of IFN-I by DCs might play an important contributory role. These findings might help us to understand the immunodeficiency of WAS. © 2012 American Academy of Allergy, Asthma & Immunology.-
dc.languageeng-
dc.relation.ispartofJournal of Allergy and Clinical Immunology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectvirus-
dc.subjectCD8 T cells-
dc.subjectType I interferon-
dc.subjectWiskott-Aldrich syndrome protein-
dc.subjectWiskott-Aldrich syndrome-
dc.subjectdiabetes-
dc.subjectdendritic cells-
dc.titleReduced type I interferon production by dendritic cells and weakened antiviral immunity in patients with Wiskott-Aldrich syndrome protein deficiency-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.jaci.2012.08.050-
dc.identifier.pmid23141740-
dc.identifier.pmcidPMC3757164-
dc.identifier.scopuseid_2-s2.0-84875231750-
dc.identifier.volume131-
dc.identifier.issue3-
dc.identifier.spage815-
dc.identifier.epage824.e2-
dc.identifier.eissn1097-6825-
dc.identifier.isiWOS:000315587800025-
dc.identifier.issnl0091-6749-

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