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

Frontiers in Immunology
Anderson Dik Wai LukYu Lung Lau

Abstract

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. 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. 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. 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 f...Continue Reading

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Citations

Aug 10, 2019·Journal of Cellular and Molecular Medicine·Bingjue YeMin Zheng
May 24, 2019·Viruses·Alexandra I Wells, Carolyn B Coyne
Oct 21, 2020·Nature Reviews. Drug Discovery·Ali A ZarrinDomagoj Vucic
Jun 25, 2021·Journal of Clinical Immunology·Ben M J ShillitoeAndrew R Gennery
Sep 10, 2021·Neurology. Neuroimmunology and Neuroinflammation·Martin S WeberMichael R Yeaman

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Methods Mentioned

BETA
GTPase
flow cytometry
RNA
PCR
Flow
ELISA

Software Mentioned

GraphPad
Prism

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