Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection

Arby Abtin; Rohit Jain; Andrew J Mitchell; Ben Roediger; Anthony J Brzoska; Shweta Tikoo; Qiang Cheng; Lai Guan Ng; Lois L Cavanagh; Ulrich H von Andrian; Michael J Hickey; Neville Firth; Wolfgang Weninger

doi:10.1038/ni.2769

Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection

Nat Immunol. 2014 Jan;15(1):45-53. doi: 10.1038/ni.2769. Epub 2013 Nov 24.

Authors

Affiliations

¹ 1] The Centenary Institute, Newtown, New South Wales, Australia. [2].
² The Centenary Institute, Newtown, New South Wales, Australia.
³ School of Biological Sciences, University of Sydney, New South Wales, Australia.
⁴ Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
⁵ Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
⁶ 1] The Centenary Institute, Newtown, New South Wales, Australia. [2] Sydney Medical School, New South Wales, Australia.
⁷ Immune Disease Institute and Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
⁸ 1] The Centenary Institute, Newtown, New South Wales, Australia. [2] Discipline of Dermatology, Sydney Medical School, New South Wales, Australia. [3] Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

PMID: 24270515
PMCID: PMC4097073
DOI: 10.1038/ni.2769

Abstract

Transendothelial migration of neutrophils in postcapillary venules is a key event in the inflammatory response against pathogens and tissue damage. The precise regulation of this process is incompletely understood. We report that perivascular macrophages are critical for neutrophil migration into skin infected with the pathogen Staphylococcus aureus. Using multiphoton intravital microscopy we showed that neutrophils extravasate from inflamed dermal venules in close proximity to perivascular macrophages, which are a major source of neutrophil chemoattractants. The virulence factor α-hemolysin produced by S. aureus lyses perivascular macrophages, which leads to decreased neutrophil transmigration. Our data illustrate a previously unrecognized role for perivascular macrophages in neutrophil recruitment to inflamed skin and indicate that S. aureus uses hemolysin-dependent killing of these cells as an immune evasion strategy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Toxins / immunology
Bacterial Toxins / metabolism
Blood Vessels / immunology
Blood Vessels / metabolism
Flow Cytometry
Gene Expression / immunology
Hemolysin Proteins / immunology
Hemolysin Proteins / metabolism
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Macrophages / immunology*
Macrophages / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Microscopy, Fluorescence, Multiphoton
Neutrophil Infiltration / immunology
Neutrophils / immunology*
Neutrophils / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Skin / blood supply
Skin / immunology*
Skin / microbiology
Staphylococcal Infections / immunology*
Staphylococcal Infections / microbiology
Staphylococcus aureus / genetics
Staphylococcus aureus / immunology
Staphylococcus aureus / metabolism
Time-Lapse Imaging / methods
Transendothelial and Transepithelial Migration / immunology
Venules / immunology
Venules / metabolism

Substances

Bacterial Toxins
Hemolysin Proteins
Luminescent Proteins
staphylococcal alpha-toxin

Grants and funding

R01 AI069259/AI/NIAID NIH HHS/United States