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Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2449-2454. doi: 10.1073/pnas.1715756115. Epub 2018 Jan 29.

Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus.

Author information

1
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4.
2
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4.
3
The Center for Molecular Biology and Medicine, Palo Alto Veterans Institute for Research, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304.
4
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305.
5
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4; pkubes@ucalgary.ca.

Abstract

Staphylococcus aureus is a skin- and respiratory tract-colonizing bacterium and is the leading cause of community-acquired skin infections. Dissemination of these bacteria into systemic circulation causes bacteremia, which has a high mortality rate. Therefore, understanding the immunologic barriers that prevent dissemination is critical to developing novel treatments. In this study, we demonstrate that an S. aureus breach across skin leads to some migration of the pathogen to the draining lymph node, but no further. While subcapsular sinus (SCS) macrophage in lymph nodes were important in detaining S. aureus, a rapid complement-dependent neutrophil recruitment (independent of the SCS macrophage) via high endothelial venules (HEVs) resulted in high numbers of neutrophils that intercepted the bacteria in the lymph nodes. Peripheral Node Addressin together with its two ligands, L-selectin and platelet P-selectin, are critical for recruiting neutrophils via the HEVs. Almost no neutrophils entered the lymph nodes via lymphatics. Neutrophils actively phagocytosed S. aureus and helped sterilize the lymph nodes and prevent dissemination to blood and other organs.

KEYWORDS:

L-selectin; Staphylococcus aureus; endothelium; lymph node; neutrophil

Comment in

PMID:
29378967
PMCID:
PMC5877924
DOI:
10.1073/pnas.1715756115
[Indexed for MEDLINE]
Free PMC Article

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