The HPV16 E7 Oncoprotein Disrupts Dendritic Cell Function and Induces the Systemic Expansion of CD11b(+)Gr1(+) Cells in a Transgenic Mouse Model.

Gabriela Damian-Morales,Rodolfo Ocadiz-Delgado,Mario Adán Moreno-Eutimio,José Bonilla-Delgado,Patricio Gariglio,Nicolás Serafín-Higuera,Genaro Rodríguez-Uribe,Paul F Lambert,Enoc M Cortés-Malagón

doi:10.1155/2016/8091353

Abstract

Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b+Gr1+ cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b+Gr1+ cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal. An increase in CD11b+Gr1+ cells was observed in the blood and skin of K14E7 mice, and molecules related to CD11b+Gr1+ chemoattraction (MCP1 and S100A9) were upregulated. Conclusions. These data suggest that the HPV16 E7 oncoprotein impairs the function and morphology of DCs and induces the systemic accumulation of CD11b+Gr1+ cells.

Highlights

High-risk human papillomaviruses (HR-HPVs) infect squamous epithelia and promote proliferative lesions
The E6 and E7 oncoproteins are the main regulators of the carcinogenic potential of HR-HPVs [2], which modulate various components of the immune system [3]
Our results demonstrate that the morphology of CD207+ cells in the mouse skin was disrupted and that migration activity was impaired

Summary

Introduction

High-risk human papillomaviruses (HR-HPVs) infect squamous epithelia and promote proliferative lesions. Persistent HR-HPV infection can eventually lead to the development of epithelial cancers (i.e., cervical, vulvar, oropharyngeal, anal, and penile) [1]. It has been reported that the hyperplastic skin of the K14E7 mouse is prone to premalignant skin lesions caused in part by a local immunosuppressive environment [5,6,7]. This phenotype is characterized by altered cytokine and chemokine expression [8, 9], which results in the recruitment of immune cells [8, 10]

Methods

Results

Conclusion