Fig. 4

Central role of dendritic cell in host immune response against virus. (1) Under the stimuli of TNF-α, IFN-γ and other molecules, DCs undergo maturation and produces type I IFN, IL-12, GM-CSF, B7 molecules (CD80 e CD86) and LFA-3 (lymphocyte function-associated antigen 3). IFN I causes NK cell activation; IL-12 and -18 promote Th1 and M1 cell profile differentiation; GM-CSF stimulates granulocyte and monocyte production and function; B7 and LFA-3 are co-stimulatory molecules of T cell in increasing inflammatory response. The Th1 profile is able to induce tumor death. (2) When DC are partially or completely immature, they play an immunosuppressive role, inducing Th2 and Treg differentiation by secreting immunomodulatory cytokines, such as TGF-β, IL-1, − 6, − 10, − 13, 23 and PD-L1. Th2 profile promotes T cell anergy and tumor establishment. (3) Similar to NK and CD8+ T cells, keratinocytes can activate DC through CD40L. (4) E-cadherin is the protein that promotes cellular interaction between LC and KC. In HPV infected tissues, E-cadherin is downregulated by the E6 oncoprotein. LCs can be activated by heparan sulfates, PAMPs, IFN-γ, TNF-α and IL-17 in order to secrete a large range of immunoprotective molecules (IFN, TNF-α, ICAM-1, AMPs, IL-1, − 6, − 10, − 18, CD40L, CCL20, CXCL9, − 10) [1, 14]