Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
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Lok, L., Dennison, T., Mahbubani, K., Saeb-Parsy, K., Chilvers, E., & Clatworthy, M. (2019). Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.. Proceedings of the National Academy of Sciences of the United States of America, 116 (38), 19083-19089. https://doi.org/10.1073/pnas.1905054116
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 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.
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
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).
WELLCOME TRUST (104384/Z/14/Z)
Arthritis Research UK (21777)
Embargo Lift Date
External DOI: https://doi.org/10.1073/pnas.1905054116
This record's URL: https://www.repository.cam.ac.uk/handle/1810/296458
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/