Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppressio
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IMMUNOLOGY AT THE UNIVERSITY OF IOWA
Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppression Katarina Kulhankova • Jessica King Wilmara Salgado-Pabo´n
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Katarina Kulhankova
Wilmara Salgado-Pabo´n
Jessica King
Ó Springer Science+Business Media New York 2014
Abstract Infectious diseases caused by Staphylococcus aureus present a significant clinical and public health problem. S. aureus causes some of the most severe hospital-associated and community-acquired illnesses. Specifically, it is the leading cause of infective endocarditis and osteomyelitis, and the second leading cause of sepsis in the USA. While pathogenesis of S. aureus infections is at the center of current research, many questions remain about the mechanisms underlying staphylococcal toxic shock syndrome (TSS) and associated adaptive immune suppression. Both conditions are mediated by staphylococcal superantigens (SAgs)—secreted staphylococcal toxins that are major S. aureus virulence factors. Toxic shock syndrome toxin-1 (TSST-1) is the SAg responsible for almost all menstrual TSS cases in the USA. TSST-1, staphylococcal enterotoxin B and C are also responsible for most cases of non-menstrual TSS. While SAgs mediate all of the hallmark features of TSS, such as fever, rash, hypotension, and multi-organ dysfunction, they are also capable of enhancing the toxic effects of endogenous endotoxin. This interaction appears to be critical in mediating the severity of TSS and related mortality. In addition, interaction between SAgs and the host immune system has been recognized to result in a unique form of adaptive immune suppression, contributing to poor outcomes of S. aureus infections. Utilizing rabbit models of S. aureus infective endocarditis, pneumonia and sepsis, and molecular genetics techniques, we aim to elucidate the mechanisms of SAg and endotoxin synergism in the pathogenesis of TSS, and examine the cellular and molecular mechanisms underlying SAg-mediated immune dysfunction. Keywords
Staphylococcal toxic shock syndrome Superantigens TSST-1 Staphylococcus aureus
Staphylococcus aureus diseases affect *500,000 individuals each year in the USA [1]. Currently, S. aureus is the leading cause of infective endocarditis (accounting for *40,000 cases/year) [1–4] and osteomyelitis, and the second leading cause of sepsis [1, 5, 6]. S. aureus also accounts for *70,000 cases of pneumonia [1, 7], more than 120,000 postsurgical infections [1, 8], and *6,000 cases of menstrual toxic shock syndrome each year in the USA [7, 9]. Contributing to these infections are both methicillin-susceptible and -resistant S. aureus. Currently, Katarina Kulhankova and Jessica King have contributed equally to this work. K. Kulhankova J. King W. Salgado-Pabo´n (&) Department of Microbiology, University of Iowa Carver College of Medicine, 51 Newton Road, Iowa City, IA 52242, USA e-mail: [email protected]
there is little understanding of S. aureus’ mechanism of pathogenesis and the nature
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