title: Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection.
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.
authors.affiliation: 1] The Centenary Institute, Newtown, New South Wales, Australia. [2].
authors.forename: Arby
authors.initials: A
authors.lastname: Abtin
authors.affiliation: 1] The Centenary Institute, Newtown, New South Wales, Australia. [2].
authors.forename: Rohit
authors.identifier: 000000024905462X
authors.initials: R
authors.lastname: Jain
authors.affiliation: 1] The Centenary Institute, Newtown, New South Wales, Australia. [2].
authors.forename: Andrew J
authors.identifier: 000000034454853X
authors.initials: AJ
authors.lastname: Mitchell
authors.affiliation: The Centenary Institute, Newtown, New South Wales, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Roediger
authors.affiliation: School of Biological Sciences, University of Sydney, New South Wales, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brzoska
authors.affiliation: The Centenary Institute, Newtown, New South Wales, Australia.
authors.forename: Shweta
authors.initials: S
authors.lastname: Tikoo
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.affiliation: 1] The Centenary Institute, Newtown, New South Wales, Australia. [2] Sydney Medical School, New South Wales, Australia.
authors.forename: Lois L
authors.initials: LL
authors.lastname: Cavanagh
authors.affiliation: Immune Disease Institute and Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hickey
authors.affiliation: School of Biological Sciences, University of Sydney, New South Wales, Australia.
authors.forename: Neville
authors.initials: N
authors.lastname: Firth
authors.affiliation: 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.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000378:metabolism; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply / Q000276:immunology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059008:Time-Lapse Imaging / Q000379:methods; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology; D014699:Venules / Q000276:immunology / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D008164:Luminescent Proteins; C021091:staphylococcal alpha-toxin