tetano
Editor, Senior Moderator
J Virol. 2014 Mar 26. [Epub ahead of print]
Animal model of respiratory syncytial virus: CD8+ T cells cause cytokine storm that is chemically tractable by sphingosine-1-phosphate 1 receptor agonist therapy.
Walsh KB1, Teijaro JR, Brock LG, Fremgen DM, Collins PL, Rosen H, Oldstone MB.
Author information
Abstract
Cytokine storm is an intensified, dysregulated, tissue injurious inflammatory response driven by cytokine and immune cell components. Cytokine storm has been well characterized during influenza virus infection whereby the amplified innate immune response is primarily responsible for pulmonary damage. Now we describe a novel event where virus-specific T cells induce cytokine storm. The paramyxovirus, pneumonia virus of mice (PVM), is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57Bl/6 mice were infected with PVM the innate inflammatory response was undetectable until day 5 post-infection, at which time CD8+ T cells infiltrated into the lung initiating cytokine storm by their production of IFN-γ and TNF-α. Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8+ T cell response resulting in diminished pulmonary disease and enhanced survival.
IMPORTANCE SECTION:
Dysregulated overly exuberant immune response termed "cytokine storm" accompanies virus-induced acute respiratory diseases (VARV), is primarily responsible for the accompanying high morbidity and mortality and can be controlled therapeutically in influenza virus infection of mice and ferrets by administration of sphingosine-1-phosphate 1 receptor (S1P1R) agonists. Here two novel findings are recorded. First, in contrast to influenza infection where cytokine storm is initiated early by the innate immune system, for pneumonia virus of mice (PVM), a model of RSV, cytokine storm is initiated late in infection by the adoptive immune response specifically by virus-specific CD8 T cells via their release of interferon-γ and TNF-α. Blockading these cytokines with neutralizing antibodies blunts cytokine storm and protects the host. Second, PVM infection is controlled by administration of S1P1R agonist.
PMID:
24672024
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24672024
Animal model of respiratory syncytial virus: CD8+ T cells cause cytokine storm that is chemically tractable by sphingosine-1-phosphate 1 receptor agonist therapy.
Walsh KB1, Teijaro JR, Brock LG, Fremgen DM, Collins PL, Rosen H, Oldstone MB.
Author information
Abstract
Cytokine storm is an intensified, dysregulated, tissue injurious inflammatory response driven by cytokine and immune cell components. Cytokine storm has been well characterized during influenza virus infection whereby the amplified innate immune response is primarily responsible for pulmonary damage. Now we describe a novel event where virus-specific T cells induce cytokine storm. The paramyxovirus, pneumonia virus of mice (PVM), is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57Bl/6 mice were infected with PVM the innate inflammatory response was undetectable until day 5 post-infection, at which time CD8+ T cells infiltrated into the lung initiating cytokine storm by their production of IFN-γ and TNF-α. Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8+ T cell response resulting in diminished pulmonary disease and enhanced survival.
IMPORTANCE SECTION:
Dysregulated overly exuberant immune response termed "cytokine storm" accompanies virus-induced acute respiratory diseases (VARV), is primarily responsible for the accompanying high morbidity and mortality and can be controlled therapeutically in influenza virus infection of mice and ferrets by administration of sphingosine-1-phosphate 1 receptor (S1P1R) agonists. Here two novel findings are recorded. First, in contrast to influenza infection where cytokine storm is initiated early by the innate immune system, for pneumonia virus of mice (PVM), a model of RSV, cytokine storm is initiated late in infection by the adoptive immune response specifically by virus-specific CD8 T cells via their release of interferon-γ and TNF-α. Blockading these cytokines with neutralizing antibodies blunts cytokine storm and protects the host. Second, PVM infection is controlled by administration of S1P1R agonist.
PMID:
24672024
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24672024