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Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.

Published version
Peer-reviewed

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Authors

Dennison, Thomas W 
Mahbubani, Krishnaa M 
Saeb-Parsy, Kourosh 
Chilvers, Edwin R 

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 show 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 dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with 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 up-regulated expression of MHCII and costimulatory 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.

Description

Keywords

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

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

116

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Medical Research Council (MR/N024907/1)
Wellcome Trust (104384/Z/14/Z)
Arthritis Research UK (21777)
L.S.C.L. was funded by Wellcome Trust (104384/Z/14/Z). M.R.C. is supported by National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Chan-Zuckerburg Initiative Human Cell Atlas Technology Development Grant, Medical Research Council New Investigator Research Grant (MR/N024907/1), Arthritis Research UK Cure Challenge Research Grant (21777), and NIHR Research Professorship (RP-2017-08- ST2-002).