title: Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release.
abstract: Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1-protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus.
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Snäll
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Linnér
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Uhlmann
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Siemens
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Heike
authors.initials: H
authors.lastname: Ibold
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Marton
authors.initials: M
authors.lastname: Janos
authors.affiliation: Department of Clinical Sciences, Lund University, S-221 84 Lund, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Linder
authors.affiliation: Institute of Medical Microbiology, Virology, Hygiene and Bacteriology, Rostock University Medical Centre, 18055 Rostock, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
authors.affiliation: Department of Clinical Sciences, Lund University, S-221 84 Lund, Sweden.
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.affiliation: Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D052243:Resistin / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000382:microbiology / Q000473:pathology; D013290:Streptococcal Infections / Q000097:blood* / Q000473:pathology; D013297:Streptococcus pyogenes
chemical_list: C499624:RETN protein, human; D052243:Resistin