Lung marginated and splenic murine resident neutrophils constitute pioneers in tissue-defense during systemic E. coli challenge
Author(s)
Type
Journal Article
Abstract
The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs slow their velocity and aggregate in clusters that enlarge as circulating neutrophils carrying E. coli stop within the microvasculature. The absolute number of splenic neutrophils does not change following challenge; however, neutrophils increase their velocity, migrate to the marginal zone (MZ) and form clusters. Irrespective of their location all neutrophils capturing heat-inactivated E. coli take on an activated phenotype showing increasing surface CD11b. At a molecular level we show that neutralization of ICAM-1 results in splenic neutrophil redistribution to the MZ under homeostasis. Following challenge, splenic levels of CXCL12 and ICAM-1 are reduced allowing neutrophils to migrate to the MZ in a CD29-integrin dependent manner, where the enlargement of splenic neutrophil clusters is CXCR2-CXCL2 dependent. We show directly molecular mechanisms that allow tissue resident neutrophils to provide the first lines of antimicrobial defense by capturing circulating E. coli and forming clusters both in the microvessels of the lung and in the parenchyma of the spleen.
Date Issued
2021-04-19
Date Acceptance
2021-03-29
Citation
Frontiers in Immunology, 2021, 12, pp.1-15
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
15
Journal / Book Title
Frontiers in Immunology
Volume
12
Copyright Statement
© 2021 Juzenaite, Secklehner, Vuononvirta, Helbawi, Mackey, Dean, Harker, Carlin, Rankin and De Filippo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000646048200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
201356/Z/16/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
intravital microscopy
E
coli challenge
neutrophil activation
intravascular neutrophils
splenic resident neutrophils
Publication Status
Published
Article Number
ARTN 597595
Date Publish Online
2021-04-19