Role of Innate Immunity against Human Papillomavirus (HPV) Infections and Effect of Adjuvants in Promoting Specific Immune Response

During the early stages of human papillomavirus (HPV) infections, the innate immune system creates a pro-inflammatory microenvironment by recruiting innate immune cells to eliminate the infected cells, initiating an effective acquired immune response. However, HPV exhibits a wide range of strategies for evading immune-surveillance, generating an anti-inflammatory microenvironment. The administration of new adjuvants, such as TLR (Toll-like receptors) agonists and alpha-galactosylceramide, has been demonstrated to reverse the anti-inflammatory microenvironment by down-regulating a number of adhesion molecules and chemo-attractants and activating keratinocytes, dendritic (DC), Langerhans (LC), natural killer (NK) or natural killer T (NKT) cells; thus, promoting a strong specific cytotoxic T cell response. Therefore, these adjuvants show promise for the treatment of HPV generated lesions and may be useful to elucidate the unknown roles of immune cells in the natural history of HPV infection. This review focuses on HPV immune evasion mechanisms and on the proposed response of the innate immune system, suggesting a role for the surrounding pro-inflammatory microenvironment and the NK and NKT cells in the clearance of HPV infections.