title: Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.
abstract: Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events.
authors.affiliation: Department of Obstetrics & Gynecology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: ddasilva@usc.edu.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Da Silva
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Carly A
authors.initials: CA
authors.lastname: Movius
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Raff
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Heike E
authors.initials: HE
authors.lastname: Brand
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Skeate
authors.affiliation: Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.affiliation: Department of Obstetrics & Gynecology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Molecular Microbiology & Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
mesh_terms: D005075:Biological Evolution; D016207:Cytokines / Q000276:immunology; D015536:Down-Regulation; D005838:Genotype; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000821:virology; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology
chemical_list: D016207:Cytokines
keywords: Antigen presentation; Antigen presenting cell; Human papillomavirus; Immune escape; Immune suppression; Langerhans cell; Migration