The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function

Katarina Kulhankova; Kyle J Kinney; Jessica M Stach; Françoise A Gourronc; Isabella M Grumbach; Aloysius J Klingelhutz; Wilmara Salgado-Pabón

doi:10.1128/IAI.00848-17

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The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function

Journal article

Open access

Peer reviewed

The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function

Katarina Kulhankova, Kyle J Kinney, Jessica M Stach, Françoise A Gourronc, Isabella M Grumbach, Aloysius J Klingelhutz and Wilmara Salgado-Pabón

Infection and immunity, Vol.86(3), e00848-17

03/2018

DOI: 10.1128/IAI.00848-17

PMCID: PMC5820935

PMID: 29229737

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Abstract

infective endocarditis (IE) is a fast-progressing and tissue-destructive infection of the cardiac endothelium. The superantigens (SAgs) toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin C (SEC), and the toxins encoded by the enterotoxin gene cluster ( ) play a novel and essential role in the etiology of IE. Recent studies indicate that SAgs act at the infection site to cause tissue pathology and promote vegetation growth. The underlying mechanism of SAg involvement has not been clearly defined. In SAg-mediated responses, immune cell priming is considered a primary triggering event leading to endothelial cell activation and altered function. Utilizing immortalized human aortic endothelial cells (iHAECs), we demonstrated that TSST-1 directly activates iHAECs, as documented by upregulation of vascular and intercellular adhesion molecules (VCAM-1 and ICAM-1). TSST-1-mediated activation results in increased monolayer permeability and defects in vascular reendothelialization. Yet stimulation of iHAECs with TSST-1 fails to induce interleukin-8 (IL-8) and IL-6 production. Furthermore, simultaneous stimulation of iHAECs with TSST-1 and lipopolysaccharide (LPS) inhibits LPS-mediated IL-8 and IL-6 secretion, even after pretreatment with either of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-1β. IL-8 suppression is not mediated by TSST-1 binding to its canonical receptor major histocompatibility complex class II (MHC-II), supporting current evidence for a nonhematopoietic interacting site on SAgs. Together, the data suggest that TSST-1 differentially regulates cell-bound and secreted markers of endothelial cell activation that may result in dysregulated innate immune responses during IE. Endothelial changes resulting from the action of SAgs can therefore directly contribute to the aggressive nature of IE and development of life-threatening complications.

Superantigens - toxicity

Interleukin-8 - genetics

Enterotoxins - toxicity

Interleukin-6 - genetics

Humans

Cells, Cultured

Bacterial Toxins - toxicity

Gene Expression Regulation - drug effects

Cell Movement - drug effects

Cell Proliferation - drug effects

Aorta - cytology

Interleukin-8 - metabolism

Interleukin-6 - metabolism

Endothelial Cells - drug effects

Details

Title: Subtitle: The Superantigen Toxic Shock Syndrome Toxin 1 Alters Human Aortic Endothelial Cell Function
Creators: Katarina Kulhankova - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Kyle J Kinney - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Jessica M Stach - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Françoise A Gourronc - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Isabella M Grumbach - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Aloysius J Klingelhutz - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Wilmara Salgado-Pabón - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA wilmara-salgado-pabon@uiowa.edu
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.86(3), e00848-17
DOI: 10.1128/IAI.00848-17
PMID: 29229737
PMCID: PMC5820935
NLM abbreviation: Infect Immun
ISSN: 0019-9567
eISSN: 1098-5522
Publisher: United States
Grant note: R01 HL108932 / NHLBI NIH HHS T32 AI007260 / NIAID NIH HHS R01 AI134692 / NIAID NIH HHS
Language: English
Date published: 03/2018
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Radiation Oncology; Internal Medicine
Record Identifier: 9984001211302771

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