T cell activation by enterotoxin gene cluster-encoded and ’classical’ Staphylococcus aureus superantigens

  • Dorothee Grumann, University of Greifswald, Germany
  • Sandra Scharf, University of Greifswald, Germany
  • Silva Holtfreter, University of Greifswald, Germany
  • Christian Kohler, University of Greifswald, Germany
  • Leif Steil, University of Greifswald, Germany
  • Susanne Engelmann, University of Greifswald, Germany
  • Uwe Voelker, University of Greifswald, Germany
  • Barbara Broeker, University of Greifswald, Germany

    • The species Staphylococcus (S.) aureus harbors 19 superantigen gene loci, six of which are located in the enterotoxin gene cluster (egc). While these egc-superantigens are far more prevalent in clinical S. aureus isolates than ’classical’ superantigens, they are no prominent cause of toxic shock. Also, neutralizing antibodies against egc-superantigens are very rare, even among carriers of egc-positive S. aureus strains. In search of an explanation for this phenomenon we have tested two non-exclusive hypotheses: (i) ’classical’ and egc-superantigens have unique intrinsic properties and drive the immune response into different directions; (ii) ’classical’ and egc-superantigens are released by S. aureus under different conditions, which shape the immune response to them.
    A systematic comparison of the T cell-activating properties of three ’classical’ (SEB, SElQ, TSST-1) and three egc-superantigens (SEI, SElM and SElQ) revealed that both induced proliferation of human PBMC with comparable potency and induced similar Th1/ Th2-cytokine signatures. These data were confirmed and extended by gene expression analysis of PBMC. The ’classical’ superantigen SEB and the egc-superantigen SEI induced very similar transcriptional changes especially of inflammation-associated gene networks, corresponding to a very strong Th1- and Th17-dominated immune response.
    In contrast, the regulation of superantigen release differed markedly between both superantigen groups. Egc-encoded proteins were secreted by S. aureus during exponential growth, while ’classical’ superantigens were released in the stationary phase.
    We conclude that the distinct biological behavior of ’classical’ and egc-superantigens is not due to their intrinsic properties, which are very similar, but caused by their differential release by S. aureus.