Uptake and intracellular trafficking of superantigens in dendritic cells

GANEM MB; DE MARZI MC; FERNÁNDEZ-LYNCH MJ; JANCIC C; VERMEULEN M; GEFFNER J; MARIUZZA RA; FERNÁNDEZ MM; MALCHIODI EL

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 8 p. 1 - 14

1932-6203

Bacterial superantigens (SAgs) are exotoxins produced mainly by Staphylococcusaureus and Streptococcus pyogenes that can cause toxic shock syndrome (TSS).According to current paradigm, SAgs interact directly and simultaneously with T cellreceptor (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 arethe most probable candidate to interact with SAgs. We demonstrate that SAgs aretaken up by mouse DCs without triggering DC maturation. SAgs were found inintracellular acidic compartment of DCs as biologically active molecules. Moreover,SAgs co-localized with EEA1, RAB-7 and LAMP-2, at different times, and were thenrecycled to the cell membrane. DCs loaded with SAgs are capable of triggering in vitrolymphocyte proliferation and, injected into mice, stimulate T cells bearing the properTCR in draining lymph nodes. Transportation and trafficking of SAgs in DCs mightincrease the local concentration of these exotoxins where they will produce the highesteffect by promoting their encounter with both MHC-II and TCR in lymph nodes, andmay explain how just a