Unc93b1-Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection

@article{Lafferty2015Unc93b1DependentET,
  title={Unc93b1-Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection},
  author={Erin I. Lafferty and Sean A. Wiltshire and Isabelle Angers and Silvia M. Vidal and Salman T. Qureshi},
  journal={Journal of Innate Immunity},
  year={2015},
  volume={7},
  pages={315 - 330}
}
Coxsackievirus strain B serotype 3 (CVB3)-induced myocarditis is an important human disease that causes permanent tissue damage and can lead to death from acute infection or long-term morbidity caused by chronic inflammation. The timing and magnitude of immune activation following CVB3 infection can mediate a positive host outcome or increase tissue pathology. To better elucidate the role of endosomal Toll-like receptor (TLR) signaling in acute CVB3 infection, we studied mice with a loss-of… 

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References

SHOWING 1-10 OF 76 REFERENCES
Myeloid differentiation factor-88 contributes to TLR9-mediated modulation of acute coxsackievirus B3-induced myocarditis in vivo.
TLDR
The MyD88/TNF-alpha axis due to TLR9 activation in the heart contributes the development of acute myocarditis but not of chronicMyocarditis.
A Role for Toll-like Receptor 3 Variants in Host Susceptibility to Enteroviral Myocarditis and Dilated Cardiomyopathy*
TLDR
The screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls, suggesting that individuals harboring these variants may have a blunted innate immune response toEnteroviral infection, leading to reduced viral clearance and an increased risk of cardiac pathology.
An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following Influenza A H1N1 infection
TLDR
A role is established for Unc93b1 and endosomal TLRs in the activation of both myeloid and lymphoid cells during the innate immune response to influenza.
UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes
TLDR
The function of the polytopic membrane protein UNC93B1 is to deliver the nucleotide-sensing receptors TLR7 and TLR9 from the ER to endolysosomes and it is shown that this protein is dispensable for ligand recognition and signal initiation by TLRs.
Myeloid Differentiation Factor-88 Plays a Crucial Role in the Pathogenesis of Coxsackievirus B3–Induced Myocarditis and Influences Type I Interferon Production
TLDR
MyD88 appears to be a key contributor to cardiac inflammation, mediating cytokine production and T-helper-1/2 cytokine balance, increasing coxsackie-adenoviral receptor and p56lck expression and viral titers after CVB3 exposure.
Over-expression of mitochondrial antiviral signaling protein inhibits coxsackievirus B3 infection by enhancing type-I interferons production
TLDR
Exogenous MAVS effectively prevents and controls CVB3 infection by modulating and promoting the production of type I IFNs and the factors that up-regulate MAVS might be an alternative prescription inCVB3-related syndromes by enhancing IFNs production.
Lipocalin 2 Is Required for Pulmonary Host Defense against Klebsiella Infection 1
TLDR
It is found that lipocalin 2 is rapidly and robustly induced by Klebsiella pneumoniae infection and is TLR4 dependent and therefore a crucial component of mucosal immune defense against pulmonary infection with K. pneumoniae.
Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis.
  • Yan Wang, Bo Gao, S. Xiong
  • Biology, Medicine
    American journal of physiology. Heart and circulatory physiology
  • 2014
TLDR
It was demonstrated that reactive oxygen species production and K(+) efflux were critical for the activation of NLRP3 inflammasome upon CVB3 infection, and modulation of inflammaome activation might represent a promising therapeutic strategy for viral myocarditis.
TRIF Is a Critical Survival Factor in Viral Cardiomyopathy
TLDR
This treatment within the viremic phase of myocarditis showed a significant long-term outcome indexed by reduced mortality, and TRIF is essential toward a cardioprotection against CVB3 infection.
IL-12 Receptor β1 and Toll-Like Receptor 4 Increase IL-1β- and IL-18-Associated Myocarditis and Coxsackievirus Replication1
TLDR
The remarkable similarities between the effects of IL-12Rβ1 and TLR4 suggest that these receptors share common downstream pathways that directly influence IL-1β and IL-18 production, and confirm that IL- 1β andIL-18 play a significant role in the pathogenesis of CB3-induced myocarditis.
...
1
2
3
4
5
...