PMID- 22273732
OWN - NLM
STAT- MEDLINE
DCOM- 20120831
LR  - 20211021
IS  - 1769-714X (Electronic)
IS  - 1286-4579 (Linking)
VI  - 14
IP  - 6
DP  - 2012 Jun
TI  - The impact of tacrolimus on the immunopathogenesis of staphylococcal 
      enterotoxin-induced systemic inflammatory response syndrome and pneumonia.
PG  - 528-36
LID - 10.1016/j.micinf.2012.01.001 [doi]
AB  - Staphylococcal superantigens (SAg) are a family of potent exotoxins produced by 
      Staphylococcus aureus. They play an important role in the pathogenesis of 
      staphylococcal shock and pneumonia by causing a robust activation of the immune 
      system and eliciting a strong surge in systemic cytokine and chemokine levels. 
      Given the biological functions of SAg, we evaluated the efficacy of tacrolimus, a 
      potent immunosuppressive agent, in the prophylaxis and therapy of staphylococcal 
      TSS and pneumonia using human leukocyte antigen (HLA)-DR3 transgenic mice. 
      Tacrolimus significantly inhibited staphylococcal SAg induced T cell activation 
      in vitro. In vivo, tacrolimus significantly suppressed the SAg-induced elevation 
      in serum cytokine and chemokine levels when given prophylactically, when 
      administered immediately or even 2 h following systemic SAg challenge. 
      Paradoxically, neither the prophylactic nor post-exposure treatment with 
      tacrolimus protected mice from lethal SAg-induced TSS. A closer examination 
      revealed that tacrolimus failed to suppress SAg-induced T cell proliferation and 
      systemic pathology, including gut dysfunction. Tacrolimus also failed to protect 
      from lethal pneumonia induced by a SAg-producing S. aureus strain. Thus, our 
      study showed that even though T cell activation by SAg plays a major role in the 
      immunopathogenesis of TSS and pneumonia, tacrolimus alone has no beneficial 
      effect.
CI  - Copyright (c) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights 
      reserved.
FAU - Tilahun, Ashenafi Y
AU  - Tilahun AY
AD  - Department of Immunology, Mayo Clinic, Rochester, MN 55906, USA.
FAU - Karau, Melissa J
AU  - Karau MJ
FAU - Clark, Chad R
AU  - Clark CR
FAU - Patel, Robin
AU  - Patel R
FAU - Rajagopalan, Govindarajan
AU  - Rajagopalan G
LA  - eng
GR  - R01 AI068741/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20120110
PL  - France
TA  - Microbes Infect
JT  - Microbes and infection
JID - 100883508
RN  - 0 (Cytokines)
RN  - 0 (Enterotoxins)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Superantigens)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Cytokines/biosynthesis/immunology
MH  - Enterotoxins/*immunology
MH  - HLA-DR3 Antigen/genetics
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology/*therapeutic use
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Transgenic
MH  - Pneumonia, Staphylococcal/*drug therapy/immunology/physiopathology
MH  - Staphylococcus aureus/*drug effects/pathogenicity
MH  - Superantigens/*immunology
MH  - Systemic Inflammatory Response Syndrome/*drug therapy/immunology/physiopathology
MH  - T-Lymphocytes/immunology
MH  - Tacrolimus/pharmacology/*therapeutic use
MH  - Treatment Outcome
EDAT- 2012/01/26 06:00
MHDA- 2012/09/01 06:00
CRDT- 2012/01/26 06:00
PHST- 2011/11/16 00:00 [received]
PHST- 2011/12/28 00:00 [revised]
PHST- 2012/01/02 00:00 [accepted]
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2012/09/01 06:00 [medline]
AID - S1286-4579(12)00004-4 [pii]
AID - 10.1016/j.micinf.2012.01.001 [doi]
PST - ppublish
SO  - Microbes Infect. 2012 Jun;14(6):528-36. doi: 10.1016/j.micinf.2012.01.001. Epub 
      2012 Jan 10.