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Toxins 2015, 7(12), 5308-5319; doi:10.3390/toxins7124886

Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model

1
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
2
Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
3
Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
Current Address: Division of Infectious Diseases, Veterans Health Service Medical Center, Seoul 05368, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Yinduo Ji
Received: 12 October 2015 / Revised: 16 November 2015 / Accepted: 1 December 2015 / Published: 8 December 2015
(This article belongs to the Collection Staphylococcus aureus Toxins)
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Abstract

Staphylococcus aureus, the most common cause of wound infection, produces several exotoxins, including superantigens (SAgs). SAgs are the potent activators of the immune system. Given this unique property, we hypothesized that SAgs produced by S. aureus in wounds would have local, as well as systemic immunologic effects. We tested our hypothesis using a novel staphylococcal skin wound infection model in transgenic mice expressing HLA-DR3. Skin wounds were left uninfected or colonized with S. aureus strains producing SAgs or an isogenic strain not producing any SAg. Animals with wounds challenged with SAg-producing S. aureus had increased morbidity and lower serum IL-17 levels compared to those challenged with the SAg non-producing S. aureus (p = 0.027 and p = 0.032, respectively). At Day 8 following microbial challenge, compared to mice with uninfected wounds, the proportion of Vβ8+CD4+ T cells was increased, while the proportion of Vβ8+CD8+ T cells was decreased only in the spleens of mice challenged with SAg-producing S. aureus (p < 0.001). No such changes were measured in mice challenged with SAg non-producing S. aureus. Lungs, livers and kidneys from mice challenged with SAg-producing, but not SAg non-producing, S. aureus showed inflammatory changes. Overall, SAg-mediated systemic immune activation in wounds harboring S. aureus may have clinical implications. View Full-Text
Keywords: HLA class II transgenic mice; Staphylococcus aureus; superantigen; skin infection; wound healing; inflammation HLA class II transgenic mice; Staphylococcus aureus; superantigen; skin infection; wound healing; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kim, C.K.; Karau, M.J.; Greenwood-Quaintance, K.E.; Tilahun, A.Y.; Krogman, A.; David, C.S.; Pritt, B.S.; Patel, R.; Rajagopalan, G. Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model. Toxins 2015, 7, 5308-5319.

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