The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia

Ashenafi Y. Tilahun, Melissa J. Karau, Chad R. Clark, Robin Patel, Govindarajan Rajagopalan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)528-536
Number of pages9
JournalMicrobes and Infection
Volume14
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Superantigens
Systemic Inflammatory Response Syndrome
Enterotoxins
Tacrolimus
Pneumonia
Staphylococcal Pneumonia
T-Lymphocytes
Chemokines
Staphylococcus aureus
Cytokines
Exotoxins
Immunosuppressive Agents
HLA Antigens
Transgenic Mice
Immune System
Shock
Cell Proliferation
Pathology

Keywords

  • Chemokines
  • Cytokines
  • HLA class II transgenic mice
  • Rodents
  • T lymphocytes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. / Tilahun, Ashenafi Y.; Karau, Melissa J.; Clark, Chad R.; Patel, Robin; Rajagopalan, Govindarajan.

In: Microbes and Infection, Vol. 14, No. 6, 06.2012, p. 528-536.

Research output: Contribution to journalArticle

Tilahun, Ashenafi Y. ; Karau, Melissa J. ; Clark, Chad R. ; Patel, Robin ; Rajagopalan, Govindarajan. / The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. In: Microbes and Infection. 2012 ; Vol. 14, No. 6. pp. 528-536.
@article{918feba92a7349e5b10b6ce5829e55d3,
title = "The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia",
abstract = "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.",
keywords = "Chemokines, Cytokines, HLA class II transgenic mice, Rodents, T lymphocytes",
author = "Tilahun, {Ashenafi Y.} and Karau, {Melissa J.} and Clark, {Chad R.} and Robin Patel and Govindarajan Rajagopalan",
year = "2012",
month = "6",
doi = "10.1016/j.micinf.2012.01.001",
language = "English (US)",
volume = "14",
pages = "528--536",
journal = "Microbes and Infection",
issn = "1286-4579",
publisher = "Elsevier Masson SAS",
number = "6",

}

TY - JOUR

T1 - The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia

AU - Tilahun, Ashenafi Y.

AU - Karau, Melissa J.

AU - Clark, Chad R.

AU - Patel, Robin

AU - Rajagopalan, Govindarajan

PY - 2012/6

Y1 - 2012/6

N2 - 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.

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.

KW - Chemokines

KW - Cytokines

KW - HLA class II transgenic mice

KW - Rodents

KW - T lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=84860431073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860431073&partnerID=8YFLogxK

U2 - 10.1016/j.micinf.2012.01.001

DO - 10.1016/j.micinf.2012.01.001

M3 - Article

VL - 14

SP - 528

EP - 536

JO - Microbes and Infection

JF - Microbes and Infection

SN - 1286-4579

IS - 6

ER -