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  4. Involvement of Pattern Recognition Receptors in Coxsackievirus B Infection of Human Islets
 
Zitierlink URN
https://nbn-resolving.de/urn:nbn:de:gbv:46-00103062-13

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

Veröffentlichungsdatum
2013-03-01
Autoren
Domsgen, Erna  
Betreuer
Mädler, Kathrin  
Gutachter
Morgan, Noel  
Zusammenfassung
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.
Schlagwörter
Pattern recognition receptors

; 

Type 1 Diabetes

; 

Coxsackievirus B

; 

Apoptosis

; 

Inflammation
Institution
Universität Bremen  
Fachbereich
Fachbereich 02: Biologie/Chemie (FB 02)  
Dokumenttyp
Dissertation
Zweitveröffentlichung
Nein
Sprache
Englisch
Dateien
Lade...
Vorschaubild
Name

00103062-1.pdf

Size

4.97 MB

Format

Adobe PDF

Checksum

(MD5):2fb04aeb257ea92e18021e7694659119

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