Superantigens produced by catheterassociated staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia

Jin Won Chung, Kerryl E. Greenwood-Quaintance, Melissa J. Karau, Ashenafi Tilahun, Shahryar Rostamkolaei Khaleghi, Vaidehi R. Chowdhary, Chella S. David, Robin Patel, Govindarajan Rajagopalan

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3 Scopus citations

Abstract

SAgs, produced by Staphylococcus aureus, play a major role in the pathogenesis of invasive staphylococcal diseases by inducing potent activation of the immune system. However, the role of SAgs, produced by S. aureus, associated with indwelling devices or tissues, are not known. Given the prevalence of deviceassociated infection with toxigenic S. aureus in clinical settings and the potency of SAgs, we hypothesized that continuous exposure to SAgs produced by catheterassociated S. aureus could have systemic consequences. To investigate these effects, we established a murine in vivo catheter colonization model. One centimeter long intravenous catheters were colonized with a clinical S. aureus isolate producing SAgs or isogenic S. aureus strains, capable or incapable of producing SAg. Catheters were subcutaneously implanted in age-matched HLA-DR3, B6, and AE<sup>o</sup> mice lacking MHC class II molecules and euthanized 7 d later. There was no evidence of systemic infection. However, in HLA-DR3 transgenic mice, which respond robustly to SSAgs, the SSAg-producing, but not the nonproducing strains, caused a transient increase in serum cytokine levels and a protracted expansion of splenic CD4<sup>+</sup> T cells expressing SSAg-reactive TCR Vβ8. Lungs, livers, and kidneys from these mice showed infiltration with CD4<sup>+</sup> and CD11b<sup>+</sup> cells. These findings were absent in B6 and AE<sup>o</sup> mice, which are known to respond poorly to SSAgs. Overall, our novel findings suggest that systemic immune activation elicited by SAgs, produced by S. aureus colonizing foreign bodies, could have clinical consequences in humans.

Original languageEnglish (US)
Pages (from-to)271-281
Number of pages11
JournalJournal of Leukocyte Biology
Volume98
Issue number2
DOIs
StatePublished - Aug 1 2015

Keywords

  • Cytokines
  • HLA class II
  • Immunopathology
  • Tlymphocytes
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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    Chung, J. W., Greenwood-Quaintance, K. E., Karau, M. J., Tilahun, A., Khaleghi, S. R., Chowdhary, V. R., David, C. S., Patel, R., & Rajagopalan, G. (2015). Superantigens produced by catheterassociated staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia. Journal of Leukocyte Biology, 98(2), 271-281. https://doi.org/10.1189/jlb.4A1214-577RR