Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus
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Updated: Feb 15, 2026
Standardized In vitro Assays to Visualize and Quantify Interactions between Human Neutrophils and Staphylococcus aureus Biofilms
Published on: June 8, 2022
Ania Bogoslowski1,2, Eugene C Butcher3,4, Paul Kubes5,2
1Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4.
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.
Insights
Staphylococcus aureus skin infections are stopped by lymph node neutrophils. These immune cells, recruited via high endothelial venules, phagocytose bacteria, preventing systemic spread and bacteremia.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Staphylococcus aureus is a major cause of skin infections and bacteremia.
- Understanding immune barriers preventing bacterial dissemination is crucial for new treatments.
Purpose of the Study:
- To investigate the immunologic barriers preventing Staphylococcus aureus dissemination from skin infections.
- To elucidate the role of lymph nodes and immune cells in controlling bacterial spread.
Main Methods:
- Tracking Staphylococcus aureus migration after skin breach.
- Analyzing immune cell recruitment to draining lymph nodes.
- Investigating the role of subcapsular sinus macrophages and neutrophils.
Main Results:
- Staphylococcus aureus migrated to draining lymph nodes but did not disseminate further.
- Subcapsular sinus macrophages detained bacteria, but complement-dependent neutrophil recruitment via high endothelial venules was key.
- Neutrophils, recruited via Peripheral Node Addressin, L-selectin, and P-selectin, phagocytosed bacteria and sterilized lymph nodes.
Conclusions:
- Lymph node neutrophils are critical in preventing Staphylococcus aureus dissemination.
- Neutrophil recruitment via high endothelial venules is essential for controlling bacterial spread.
- Targeting neutrophil recruitment may offer novel therapeutic strategies against S. aureus infections.
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