Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes
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Accepted version
Supplementary information
Author(s)
Type
Journal Article
Abstract
Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we showed that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics respectively, and formed interactions with DCs in LNs. Murine and human LN neutrophils had a distinct phenotype compared to circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils upregulated expression of MHCII and co-stimulatory molecules, and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory
Date Issued
2019-09-17
Date Acceptance
2019-08-12
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (38), pp.19083-19089
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
19083
End Page
19089
Journal / Book Title
Proceedings of the National Academy of Sciences of the United States of America
Volume
116
Issue
38
Copyright Statement
Copyright © 2019 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
neutrophils
lymph node
homeostasis
BONE-MARROW
KINETICS
SURVIVAL
REVEALS
TRAFFICKING
CD4(+)
MICE
CSF
homeostasis
lymph node
neutrophils
Animals
CD4-Positive T-Lymphocytes
Cell Movement
Dendritic Cells
Female
Histocompatibility Antigens Class II
Humans
Interferon-gamma
Lymph Nodes
Lymphatic Vessels
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Neutrophils
Phenotype
Lymph Nodes
Dendritic Cells
Neutrophils
CD4-Positive T-Lymphocytes
Lymphatic Vessels
Animals
Mice, Inbred C57BL
Humans
Mice
Histocompatibility Antigens Class II
Lymphocyte Activation
Cell Movement
Phenotype
Female
Interferon-gamma
Publication Status
Published
Date Publish Online
2019-09-04