title: Platelet-Dependent Neutrophil Function Is Dysregulated by M Protein from Streptococcus pyogenes.
abstract: Platelets are rapidly responsive sentinel cells that patrol the bloodstream and contribute to the host response to infection. Platelets have been reported to form heterotypic aggregates with leukocytes and may modulate their function. Here, we have investigated platelet-neutrophil complex formation and neutrophil function in response to distinct agonists. The endogenous platelet activator thrombin gave rise to platelet-dependent neutrophil activation, resulting in enhanced phagocytosis and bacterial killing. Streptococcus pyogenes is an important causative agent of severe infectious disease, which can manifest as sepsis and septic shock. M1 protein from S. pyogenes also mediated platelet-neutrophil complex formation; however, these neutrophils were dysfunctional and exhibited diminished chemotactic ability and bacterial killing. This reveals an important agonist-dependent neutrophil dysfunction during platelet-neutrophil complex formation and highlights the role of platelets during the immune response to streptococcal infection.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Sinéad M
authors.initials: SM
authors.lastname: Hurley
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Kahn
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Nordenfelt
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden oonagh.shannon@med.lu.se.
authors.forename: Oonagh
authors.initials: O
authors.lastname: Shannon
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D015539:Platelet Activation / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology* / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000276:immunology / Q000378:metabolism; D013917:Thrombin / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein; D013917:Thrombin