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Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19083-19089. doi: 10.1073/pnas.1905054116. Epub 2019 Sep 4.

Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.

Author information

1
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
2
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.
3
Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.
4
National Institute of Health Research Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, United Kingdom.
5
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; e.chilvers@imperial.ac.uk mrc38@medschl.cam.ac.uk.
6
National Heart and Lung Institute, Imperial College London, London W12 0NN, United Kingdom.
7
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom; e.chilvers@imperial.ac.uk mrc38@medschl.cam.ac.uk.

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.

KEYWORDS:

homeostasis; lymph node; neutrophils

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