Neutrophil Dysfunction in the Airways of Children with Acute Respiratory Failure Due to Lower Respiratory Tract Viral and Bacterial Coinfections

Scientific Reports
Jocelyn R GrunwellRabindra Tirouvanziam

Abstract

Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrated into the aspirate fluid from children with bacterial coinfection showed decreased respiratory burst and killing activity against H. influenzae and S. aureus compared to those transmigrated into the aspirate fluid from children without bacterial coi...Continue Reading

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Citations

Feb 6, 2020·International Journal of Molecular Sciences·Vincent D GiacaloneRabindra Tirouvanziam
Sep 20, 2020·International Journal of Molecular Sciences·Piotr WójcikElżbieta Skrzydlewska
Feb 27, 2021·Thorax·Helena CrisfordJodie L Simpson
Jan 27, 2021·Infection and Immunity·Shaunna R SimmonsElsa N Bou Ghanem
Mar 25, 2021·Mucosal Immunology·Cecilia Johansson, Freja C M Kirsebom
Apr 4, 2021·International Journal of Molecular Sciences·Bijean D FordRabindra Tirouvanziam
May 6, 2021·Cell Reports Medicine·Camilla MargaroliRabindra Tirouvanziam
May 8, 2021·Frontiers in Pharmacology·Vikas P SukhatmeVidula V Sukhatme
May 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jun ZhaoYuval Kluger
Jul 3, 2021·Vaccines·Sneha T GeorgeCaitlin E Mullarkey
Jun 22, 2021·Critical Care Explorations·Jocelyn R GrunwellRishikesan Kamaleswaran
Nov 28, 2021·Scientific Reports·Jocelyn R GrunwellRishikesan Kamaleswaran

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Methods Mentioned

BETA
flow cytometry
flow
Fluorescence
enzyme-linked immunosorbent assays
ELISA
PMA
bronchoalveolar lavage
lavage

Software Mentioned

FlowJo
JMP Pro
PELOD
Prism

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