Abstract
Bacterial superantigens (SAgs) are exotoxins produced mainly by Staphylococcus aureus and Streptococcus pyogenes that can cause toxic shock syndrome (TSS). According to current paradigm, SAgs interact directly and simultaneously with T cell receptor (TCR) on the T cell and MHC class II (MHC-II) on the antigen-presenting cell (APC), thereby circumventing intracellular processing to trigger T cell activation. Dendritic cells (DCs) are professional APCs that coat nearly all body surfaces and are the most probable candidate to interact with SAgs. We demonstrate that SAgs are taken up by mouse DCs without triggering DC maturation. SAgs were found in intracellular acidic compartment of DCs as biologically active molecules. Moreover, SAgs co-localized with EEA1, RAB-7 and LAMP-2, at different times, and were then recycled to the cell membrane. DCs loaded with SAgs are capable of triggering in vitro lymphocyte proliferation and, injected into mice, stimulate T cells bearing the proper TCR in draining lymph nodes. Transportation and trafficking of SAgs in DCs might increase the local concentration of these exotoxins where they will produce the highest effect by promoting their encounter with both MHC-II and TCR in lymph nodes, and may explain how just a few SAg molecules can induce the severe pathology associated with TSS.
Highlights
Bacterial superantigens (SAgs) comprise a large family of exotoxins produced mainly by Staphylococcus aureus and Streptococcus pyogenes [1]
In order to determine whether mouse Dendritic cells (DCs) are able to internalize SAgs, cells were incubated with FITC-labeled S. aureus
Cells were analyzed by FACs in the presence of trypan blue, and compared to non-pulsed DCs as control
Summary
Bacterial superantigens (SAgs) comprise a large family of exotoxins produced mainly by Staphylococcus aureus and Streptococcus pyogenes [1]. SAgs produced by S. aureus include SEA through SER, excluding F, and TSST-1, and constitute the major cause of food poisoning in humans. These SAgs induce diarrhea, emesis, and systemic intoxication, leading to a severe condition known as toxic shock syndrome (TSS). This syndrome includes high fever of sudden outbreak, rash, diarrhea and, in some cases, renal and lung failure that may end in death. S. pyogenes SAgs including SPEA and SSA, cause scarlet fever, pyrogenicity, and a fulminant illness known as streptococcal TSS, which displays features similar to staphylococcus TSS. SAgs are classified as Category B priority agents by the Centers for Disease Control and Prevention because of their potential use in bioterrorism and biological warfare
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