PMID- 23799083
OWN - NLM
STAT- MEDLINE
DCOM- 20140130
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 6
DP  - 2013
TI  - Uptake and intracellular trafficking of superantigens in dendritic cells.
PG  - e66244
LID - 10.1371/journal.pone.0066244 [doi]
LID - e66244
AB  - 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.
FAU - Ganem, Maria B
AU  - Ganem MB
AD  - Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de 
      Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina.
FAU - De Marzi, Mauricio C
AU  - De Marzi MC
FAU - Fernandez-Lynch, Maria J
AU  - Fernandez-Lynch MJ
FAU - Jancic, Carolina
AU  - Jancic C
FAU - Vermeulen, Monica
AU  - Vermeulen M
FAU - Geffner, Jorge
AU  - Geffner J
FAU - Mariuzza, Roy A
AU  - Mariuzza RA
FAU - Fernandez, Marisa M
AU  - Fernandez MM
FAU - Malchiodi, Emilio L
AU  - Malchiodi EL
LA  - eng
GR  - R03 TW007972/TW/FIC NIH HHS/United States
GR  - TW007972/TW/FIC NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130614
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Enterotoxins)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Superantigens)
RN  - 0 (T-cell receptor Vbeta 8.2)
RN  - 0 (Vesicular Transport Proteins)
RN  - 0 (early endosome antigen 1)
RN  - 0 (enterotoxin G, staphylococcal)
RN  - 0 (enterotoxin I, staphylococcal)
RN  - 0 (rab7 GTP-Binding Proteins)
RN  - 0 (streptococcal superantigen SSA)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/immunology/*metabolism
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/immunology/*metabolism
MH  - Endocytosis
MH  - Endosomes/metabolism
MH  - Enterotoxins/immunology/*metabolism
MH  - Lymphocyte Activation
MH  - Lymphocytes/immunology/metabolism
MH  - Lysosomal-Associated Membrane Protein 2/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Peptide Fragments/metabolism
MH  - Phenotype
MH  - Protein Transport
MH  - Receptors, Antigen, T-Cell, alpha-beta/metabolism
MH  - Superantigens/immunology/*metabolism
MH  - Transport Vesicles/metabolism
MH  - Vesicular Transport Proteins/metabolism
MH  - rab GTP-Binding Proteins/metabolism
MH  - rab7 GTP-Binding Proteins
PMC - PMC3682983
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/06/27 06:00
MHDA- 2014/01/31 06:00
PMCR- 2013/06/14
CRDT- 2013/06/27 06:00
PHST- 2012/09/02 00:00 [received]
PHST- 2013/05/07 00:00 [accepted]
PHST- 2013/06/27 06:00 [entrez]
PHST- 2013/06/27 06:00 [pubmed]
PHST- 2014/01/31 06:00 [medline]
PHST- 2013/06/14 00:00 [pmc-release]
AID - PONE-D-12-26835 [pii]
AID - 10.1371/journal.pone.0066244 [doi]
PST - epublish
SO  - PLoS One. 2013 Jun 14;8(6):e66244. doi: 10.1371/journal.pone.0066244. Print 2013.