Infection by high-risk HPV types is necessary but not sufficient for progression to cancer. In fact, the majority of HPV infections do not lead to cytological anomalies or cancer but only a small percentage (10-15%) persist and promote the development of low and high-grade lesions. It is known that to persist HPV must escape the host immune system and persistence could be due to an impaired IFN-system activation in the infected individual. In literature, most studies were conducted in cell lines with constitutively oncogenes expression, whereas in vivo, the majority of HPV infections that resolve with time have a transient oncogene expression. To clarify the role of innate immune response, we analysed, for the first time, the expression of several TLRs (TLR2, TLR3, TLR4, TLR7 and TLR9), the IFN lambda pathways (INF-lambda 1, INF-lambda II, the IFN-lambda receptors), and the activation of several IFN induced genes (ISG15, MxA and p56) in HPV positive and negative cervical cells from 154 patients. The expression levels of TLR2, TLR3, TLR4 and TLR7 resulted highly variable both in HPV negative and in HPV positive patients. Differently, TLR9 was activated at different levels during HPV infection, with a tendency to be higher in LR-HPV infected women and significantly higher in patients with HPV persistent infection. Furthermore, we correlated TLRs expression with histological grade of lesions; TLR7 and TLR9 increased with the histopathological grade, but TLR9 in patients with persistent HPV infection was greater then in patients with CIN II or worse lesion, independently of lesions grade We hypothesize that the inability to clear HPV DNA after one year could be a risk factor to later develop high-grade lesions due to the persistence of the virus and the high levels of TLR9. IFN lambda 1 was expressed at higher level in patients with LR HPV infection compared to HR HPV and negative and we observed the same trend for IFN lambda 2/3. The elevated expression level of IL28R in patients with LR HPV infection respect to the other study groups confirmed the data obtained with IFN-lambda.

study on virological and immunological factors involved in determining the course of HPV anogenital infection / Cannella, Fabiana. - (2013 Feb 12).

study on virological and immunological factors involved in determining the course of HPV anogenital infection

CANNELLA, FABIANA
12/02/2013

Abstract

Infection by high-risk HPV types is necessary but not sufficient for progression to cancer. In fact, the majority of HPV infections do not lead to cytological anomalies or cancer but only a small percentage (10-15%) persist and promote the development of low and high-grade lesions. It is known that to persist HPV must escape the host immune system and persistence could be due to an impaired IFN-system activation in the infected individual. In literature, most studies were conducted in cell lines with constitutively oncogenes expression, whereas in vivo, the majority of HPV infections that resolve with time have a transient oncogene expression. To clarify the role of innate immune response, we analysed, for the first time, the expression of several TLRs (TLR2, TLR3, TLR4, TLR7 and TLR9), the IFN lambda pathways (INF-lambda 1, INF-lambda II, the IFN-lambda receptors), and the activation of several IFN induced genes (ISG15, MxA and p56) in HPV positive and negative cervical cells from 154 patients. The expression levels of TLR2, TLR3, TLR4 and TLR7 resulted highly variable both in HPV negative and in HPV positive patients. Differently, TLR9 was activated at different levels during HPV infection, with a tendency to be higher in LR-HPV infected women and significantly higher in patients with HPV persistent infection. Furthermore, we correlated TLRs expression with histological grade of lesions; TLR7 and TLR9 increased with the histopathological grade, but TLR9 in patients with persistent HPV infection was greater then in patients with CIN II or worse lesion, independently of lesions grade We hypothesize that the inability to clear HPV DNA after one year could be a risk factor to later develop high-grade lesions due to the persistence of the virus and the high levels of TLR9. IFN lambda 1 was expressed at higher level in patients with LR HPV infection compared to HR HPV and negative and we observed the same trend for IFN lambda 2/3. The elevated expression level of IL28R in patients with LR HPV infection respect to the other study groups confirmed the data obtained with IFN-lambda.
12-feb-2013
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/916767
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