Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation.
Human papillomavirus (HPV) infection of cervical epithelium is linked to the generation of cervical cancer. Although most women infected with HPV clear their lesions, the long latency period from infection to resolution indicates that HPV evolved immune escape mechanisms. Dendritic cells, which are targeted by vaccination procedures, incubated with HPV virus-like particles induce an HPV-specific immune response. Langerhans cells (LC), which are located at the sites of primary infection, do not induce a response implicating the targeting of LC as an immune escape mechanism used by HPV. LC incubated with HPV virus-like particles up-regulate the phosphoinositide 3-kinase (PI3-K) pathway and down-regulate MAPK pathways. With the inhibition of PI3-K and incubation with HPV virus-like particles, LC initiate a potent HPV-specific response. PI3-K activation in LC defines a novel escape mechanism used by HPV, and PI3-K inhibition may serve as an effective clinical target to enhance HPV immunity.
Fausch
Steven C
SC
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, 90089, USA.
Fahey
Laura M
LM
Da Silva
Diane M
DM
Kast
W Martin
WM
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology; D007801:Langerhans Cells / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D027383:Papillomaviridae / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D014771:Virion / Q000276:immunology
D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010749:Phosphoprotein Phosphatases; D011493:Protein Kinase C