The role of Fas/FasL in maintenance of vaginal epi.. (FasVag/HSV-2)
The role of Fas/FasL in maintenance of vaginal epithelium integrity during HSV-2 infection
Start date: Jan 1, 2012,
End date: Dec 31, 2013
Genital herpes is the main cause of genital ulcers worldwide. Ulcerations resulting from recurrent HSV-2 infection consists one of the most common factors influencing integrity and functioning of genital mucosa and heighten the risk of HIV transmission. There are several types of cell death, of which apoptosis is a physiological process necessary for vaginal epithelium turnover during an oestrous cycle. Cell death receptors, such as Fas receptor together with its natural ligand, FasL, have been shown to participate in vaginal regression by inducing apoptosis. The Fas/FasL system plays an important role in skin and epithelial homeostasis, carcinogenesis and inflammatory skin diseases. Considering the fact that HSV-2 infection heightens the risk of other STDs, such as HIV and may involve exacerbation of apoptosis and inflammatory mechanisms, the idea of this project is to further explore the role of Fas/FasL system in regulation of the inflammatory and immune response and infection resolution during HSV-2 genital infection. The project will use the mouse model of genital herpes in the mice lacking Fas and FasL genes to compare inflammatory cytokines/chemokines production, local early immune response and efficiency of genital infection with the HSV-2 infection in wild-type mice. Further, the project will use the knowledge gained in an animal model to test how HSV-2 facilitates mucosal HIV-1 infection by eliciting inflammatory states in the in vitro human epithelial model. The will use up-to day techniques such as flow cytometry, DNA microarray assays, confocal microscope visualisation system and RNA intereference technology. The knowledge and expertise gained through this training project should help to designate and develop a new treatment methods (microbicides) in sexually transmitted diseases as well as to help a fellow to develop further independence as researcher.
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