Increased susceptibility of airway epithelial cells from ataxia-telangiectasia to S. pneumoniae infection due to oxidative damage and impaired innate immunity

Scientific Reports
Abrey J YeoMartin F Lavin

Abstract

Respiratory disease is a major cause of morbidity and mortality in patients with ataxia-telangiectasia (A-T) who are prone to recurrent sinopulmonary infections, bronchiectasis, pulmonary fibrosis, and pulmonary failure. Upper airway infections are common in patients and S. pneumoniae is associated with these infections. We demonstrate here that the upper airway microbiome in patients with A-T is different from that to healthy controls, with S. pneumoniae detected largely in patients only. Patient-specific airway epithelial cells and differentiated air-liquid interface cultures derived from these were hypersensitive to infection which was at least in part due to oxidative damage since it was partially reversed by catalase. We also observed increased levels of the pro-inflammatory cytokines IL-8 and TNF-α (inflammasome-independent) and a decreased level of the inflammasome-dependent cytokine IL-β in patient cells. Further investigation revealed that the ASC-Caspase 1 signalling pathway was defective in A-T airway epithelial cells. These data suggest that the heightened susceptibility of these cells to S. pneumoniae infection is due to both increased oxidative damage and a defect in inflammasome activation, and has implications f...Continue Reading

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Citations

Sep 12, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Rachel WarrenMichael A O'Reilly
Aug 15, 2020·Expert Review of Clinical Immunology·Parisa AmirifarAsghar Aghamohammadi
Feb 9, 2021·The Journal of Allergy and Clinical Immunology. in Practice·Oded Shamriz
Jun 3, 2021·Viruses·Ana Méndez-EchevarríaCristina Calvo

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Methods Mentioned

BETA
PCR
scrapings
AlphaLISA
Assay

Software Mentioned

AxioVision
GraphPad
ALDEx2
AlphaLISA
GraphPad Prism
Calypso

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