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R848 or influenza virus can induce potent innate immune responses in the lungs of neonatal mice

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Title: R848 or influenza virus can induce potent innate immune responses in the lungs of neonatal mice
Authors: Johansson, C
Makris, S
Item Type: Journal Article
Abstract: Innate immune responses are important to protect the neonatal lung, which becomes exposed to commensal and pathogenic microorganisms immediately after birth, at a time when both the lung and the adaptive immune system are still developing. How immune cells in the neonatal lung respond to innate immune stimuli, including toll-like receptor (TLR) agonists, or viruses, is currently unclear. To address this, adult and neonatal mice were intranasally administered with various innate immune stimuli, respiratory syncytial virus (RSV) or influenza virus and cytokine and chemokine levels were quantified. The neonatal lungs responded weakly to RSV and most stimuli but more strongly than adult mice to R848 and influenza virus, both of which activate TLR7 and the inflammasome. Notably, neonatal lungs also contained higher levels of cAMP, a secondary messenger produced following adenosine receptor signaling, than adult lungs and increased responsiveness to R848 was observed in adult mice when adenosine was coadministered. Our data suggest that the neonatal lung may respond preferentially to stimuli that coactivate TLR7 and the inflammasome and that these responses may be amplified by extracellular adenosine. Improved understanding of regulation of immune responses in the neonatal lung can inform the development of vaccine adjuvants for the young.
Issue Date: 23-Jun-2020
Date of Acceptance: 27-May-2020
URI: http://hdl.handle.net/10044/1/80737
DOI: 10.1038/s41385-020-0314-6
ISSN: 1933-0219
Publisher: Springer Nature [academic journals on nature.com]
Start Page: 267
End Page: 276
Journal / Book Title: Mucosal Immunology
Volume: 14
Copyright Statement: © 2020 Springer Nature Limited.
Sponsor/Funder: Medical Research Council (MRC)
Rosetrees Trust
Rosetrees Trust
National Heart and Lung Institute Foundation
Rosetrees Trust
Funder's Grant Number: G0800311
M370
A442
Spiros Makris
M370-F1
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
RESPIRATORY SYNCYTIAL VIRUS
ALVEOLAR MACROPHAGES
ANTIVIRAL RESPONSES
RNA
INFLAMMASOME
RECOGNITION
INFECTION
CYTOKINE
CHILDREN
RECEPTOR
Immunology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2020-06-23
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine