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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.

SUBMITTER: Hurley SM

PROVIDER: S-EPMC4534654 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Platelet-Dependent Neutrophil Function Is Dysregulated by M Protein from Streptococcus pyogenes.

Hurley Sinéad M SM Kahn Fredrik F Nordenfelt Pontus P Mörgelin Matthias M Sørensen Ole E OE Shannon Oonagh O

Infection and immunity 20150622 9

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 bacte ...[more]

PMID: 26099589

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Project description:BackgroundConflicting results have been reported on platelet activity ex vivo and responsiveness in vitro among patients with COVID-19 with or without thromboembolic complications.ObjectivesTo assess platelet reactivity in patients with moderate disease at early stages of COVID-19.MethodsWe performed a prospective, descriptive analysis of 100 consecutive patients presenting with suspected SARS-CoV-2 infection at University Medical Center Freiburg during the first or second wave of the pandemic. Following polymerase chain reaction testing and compliance with study inclusion criteria, 20 SARS-CoV-2-positive and 55 SARS-CoV-2-negative patients (serving as patient controls) were enrolled. In addition, 15 healthy subjects were included. Platelet reactivity was assessed using whole-blood impedance aggregometry and flow cytometry in response to various agonists.ResultsPlatelet aggregation was significantly impaired in the patients with COVID-19 compared with that in the patient controls or healthy subjects. The reduced platelet responsiveness in the patients with COVID-19 was associated with impaired activation of GPIIb/IIIa (αIIbβ3). In contrast, low expression of P-selectin at baseline and intact secretion upon stimulation in vitro suggest that no preactivation in vivo, leading to "exhausted" platelets, had occurred. The proportion of circulating platelet-neutrophil complexes was significantly higher in the patients with COVID-19 (mean ± SD, 41% ± 13%) than in the patient controls (18% ± 7%; 95% CI, 11.1-34.1; P = .0002) or healthy subjects (17% ± 4%; 95% CI, 13.8-33.8; P < .0001). An analysis of neutrophil adhesion receptors revealed upregulation of CD11b (α-subunit of αMβ2) and CD66b (CEACAM8) but not of CD162 (PSGL-1) in the patients with COVID-19.ConclusionDespite reduced platelet responsiveness, platelet-neutrophil complexes are increased at early stages of moderate disease. Thus, this cellular interaction may occur during COVID-19 without preceding platelet activation.

Dataset Information

Platelet-Dependent Neutrophil Function Is Dysregulated by M Protein from Streptococcus pyogenes.

Publications

Platelet-Dependent Neutrophil Function Is Dysregulated by M Protein from Streptococcus pyogenes.

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