IRUS Total

Neutrophils drive alveolar macrophage IL-1β release during respiratory viral infection

File Description SizeFormat 
thoraxjnl-2017-210010.full.pdfPublished version7.53 MBAdobe PDFView/Open
Title: Neutrophils drive alveolar macrophage IL-1β release during respiratory viral infection
Authors: Peiró, T
Patel, DF
Akthar, S
Gregory, LG
Pyle, CJ
Harker, JA
Birrell, MA
LLoyd, CM
Snelgrove, RJ
Item Type: Journal Article
Abstract: Background Alveolar macrophages are sentinels of the airways that must exhibit immune restraint to innocuous antigens but elicit a robust inflammatory response to pathogenic threats. How distinction between these dichotomous functions is controlled is poorly defined. Neutrophils are the first responders to infection, and we hypothesised that they may free alveolar macrophages from their hyporesponsive state, promoting their activation. Activation of the inflammasome and interleukin (IL)-1β release is a key early inflammatory event that must be tightly regulated. Thus, the role of neutrophils in defining inflammasome activation in the alveolar macrophage was assessed. Methods Mice were infected with the X31 strain of influenza virus and the role of neutrophils in alveolar macrophage activation established through administration of a neutrophil-depleting (1A8) antibody. Results Influenza elicited a robust IL-1β release that correlated (r=0.6849; p<0.001) with neutrophil infiltrate and was ablated by neutrophil depletion. Alveolar macrophages were shown to be the prominent source of IL-1β during influenza infection, and virus triggered the expression of Nod-like receptor protein 3 (NLRP3) inflammasome and pro-IL-1β in these cells. However, subsequent activation of the inflammasome complex and release of mature IL-1β from alveolar macrophages were critically dependent on the provision of a secondary signal, in the form of antimicrobial peptide mCRAMP, from infiltrating neutrophils. Conclusions Neutrophils are critical for the activation of the NLRP3 inflammasome in alveolar macrophages during respiratory viral infection. Accordingly, we rationalise that neutrophils are recruited to the lung to confront a viable pathogenic threat and subsequently commit alveolar macrophages to a pro-inflammatory phenotype to combat infection.
Issue Date: 27-Oct-2017
Date of Acceptance: 8-Oct-2017
URI: http://hdl.handle.net/10044/1/51722
DOI: https://dx.doi.org/10.1136/thoraxjnl-2017-210010
ISSN: 1468-3296
Publisher: BMJ Publishing Group
Start Page: 546
End Page: 556
Journal / Book Title: Thorax
Volume: 73
Copyright Statement: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: G1000758
Keywords: innate immunity
macrophage biology
neutrophil biology
respiratory infection
viral infection
1103 Clinical Sciences
Respiratory System
Publication Status: Published
Appears in Collections:National Heart and Lung Institute