Epithéliums, cellules de Langherans et infections virales.

Abstract

Les cellules de Langerhans sont des cellules dendritiques de l’épiderme et des épithéliums stratifiés des muqueuses orales et génitales. Placées en sentinelle dans ces tissus et présentant les antigènes aux lymphocytes, elles jouent un rôle fondamental dans l’immunité cutanée et muqueuse et sont aptes à réagir à toutes sortes d’agressions, en particulier virales : virus de l’immunodéficience humaine (VIH), papillomavirus humains (HPV) et virus Herpes simplex (HSV). La peau est, chez l’homme, le site préférentiel d’infection par HSV et les types bénins de HPV tandis que les muqueuses orales et génitales sont très sensibles au VIH, à HSV et aux types oncogéniques d’HPV 16 et 18. Les cellules de Langerhans expriment CD4, le récepteur principal du VIH, et leur intervention est essentielle dans l’infection. Elles répliquent le virus puis le transportent, lui ou son génome, jusqu’aux ganglions lymphatiques. Associées aux lymphocytes T CD4+, elles se multiplient au début de l’infection, puis leur nombre décroît avec la même dynamique que celle des lymphocytes CD4+.

Langerhans cells (LC) are dendritic cells of normal squamous epithelia including skin, oral and genital mucosa. They play a crucial role in immune reactions, especially after viral infections such as human immune deficiency virus (HIV), papillomaviruses (HPV) and herpes simplex viruses (HSV1 and HSV2). LC are usually identified by their expression of CD1a antigen; they are mainly localized within basal and spinous epithelial layers. Normal mucosa differ from skin by the lack of horney layer and the presence of a high number of T lymphocytes in the epithelium. In human, skin is the preferential site of infection by HSV and by benign HPV types whereas oral and genital mucosa are very sensitive to HIV, HSV and oncogenic HPV types 16 and 18. It is now admitted that HSV and HPV penetrate into the skin through microtrauma whereas the virus route of entry is direct in mucosa. Target cells are epithelial cells for HPV and HSV and T cells for HIV. Epithelial LC can be infected by HIV and HSV and they further transport the complete virus or the virus genome to lymph nodes. Viral infections are responsible of drastic modifications of LC phenotype due to the changes in microenvironment and local production of cytokines from epithelial and/or inflammatory cells. For HIV, HSV and HPV, memory T cells are essential in controlling persisting infection in the host. LC contribute to the local immune reactions against the infected cells or tumoral cells derived from the infection. Their depletion and their migration into the stroma are common features to HIV, HPV and HSV infections which may account for a defect of the host immune response to the viruses. Vaccination with LC carrying specific antigens could be an appropriate approach to eliminate infected or tumoral cells derived from these three infections. [References: 41]