The enteropathogenic bacteria Salmonella are the main cause of food borne gastroenteritis worldwide. The activation of Toll-like receptor 4 (TLR4) by LPS triggers an immune response to counter infection. Signaling by TLR4 requires the adaptor proteins, TIRAP and TRAM. Recruitment and activation of these molecules is dependent on the membrane lipid, PIP2. The Salmonella effector, SigD, is a 4-phosphatase that depletes PIP2 from the host plasma membrane during invasion. Thus, we investigated if SigD could lead to the interruption of the TLR4 pathway. We observed that SigD expression caused the disappearance of TIRAP from the Salmonella containing vacuoles (SCVs) in HeLa cells. Furthermore, we demonstrated that SigD attenuates NF-κB activation, implicating SigD in the disruption of the MyD88 dependent pathway. In addition, the observed inhibition of PKCε phosphorylation suggests SigD may also block the other branch of the TLR4 signaling cascade, the MyD88 independent pathway.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29614 |
| Date | 25 August 2011 |
| Creators | Saravia, Sandy |
| Contributors | Terebiznik, Mauricio |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis, Video |
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