Skip navigation
SuUB logo
DSpace logo

  • Home
  • Institutions
    • University of Bremen
    • City University of Applied Sciences
    • Bremerhaven University of Applied Sciences
  • Sign on to:
    • My Media
    • Receive email
      updates
    • Edit Account details

Citation link: http://nbn-resolving.de/urn:nbn:de:gbv:46-00103062-13
00103062-1.pdf
OpenAccess
 
copyright

Involvement of Pattern Recognition Receptors in Coxsackievirus B Infection of Human Islets


File Description SizeFormat
00103062-1.pdf5.09 MBAdobe PDFView/Open
Other Titles: Beteiligung von Pattern Recognition Rezeptoren während einer Coxsackievirus B Infektion von Humanen Inseln
Authors: Domsgen, Erna 
Supervisor: Mädler, Kathrin 
1. Expert: Mädler, Kathrin 
2. Expert: Morgan, Noel 
Abstract: 
T1DM is an autoimmune disease in which beta-cells are selectively destroyed by the immune system. As consequence of beta-cell destruction insulin levels decline resulting in elevated blood glucose levels. The disease is highly associated with genetic susceptibility. Over the last decades the overall incidence is rising especially in children under the age of 5. This increase is too big to be explained by genetic factors only, suggesting that environmental factors contribute to the manifestation of the disease. Such environmental factors may be viral infections, which have been associated with T1DM for many years. Epidemiological studies and analysis of pancreatic tissue samples show the clear involvement of EVs and among those, coxsackievirus B (CVB) in T1DM. In the present study isolated human islets were infected with two serotypes CVB3 and CVB4 and molecular mechanisms of infections were investigated. Infections with both viruses showed that mainly beta-cells were infected which resulted in specific beta-cell apoptosis and impaired beta-cell function. Gene expression analysis revealed that upon CVB3 and CVB4 infections genes encoding pro-inflammatory proteins were highly expressed, especially those of CXCL10 and IFNb. Such induction of inflammatory related genes is mediated by pattern recognition receptors (PRR´s). The present study showed the binding or CVB3 and CVB4 RNA to PKR and in addition to the PRR´s TLR3 and TLR7. TLR3 depleted human islets infected with CVB3 and CVB4, showed lower expression levels of cytokine and chemokine genes, especially of CXCL10 and IFNb genes, indicating that induction of gene expression was TLR3 mediated. In addition, TLR3 depleted and CVB3 and CVB4 infected human islets showed less apoptosis, suggesting that the TLR3 pathway was involved in virus-induced beta-cell death.
Keywords: Pattern recognition receptors, Type 1 Diabetes, Coxsackievirus B, Apoptosis, Inflammation
Issue Date: 1-Mar-2013
Type: Dissertation
URN: urn:nbn:de:gbv:46-00103062-13
Institution: Universität Bremen 
Faculty: FB2 Biologie/Chemie 
Appears in Collections:Dissertationen

  

Page view(s)

18
checked on Jan 19, 2021

Download(s)

3
checked on Jan 19, 2021

Google ScholarTM

Check


Items in Media are protected by copyright, with all rights reserved, unless otherwise indicated.

Legal notice -Feedback -Data privacy
Media - Extension maintained and optimized by Logo 4SCIENCE