Toll-Like Receptors in Human Papillomavirus Infection
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REVIEW
Toll-Like Receptors in Human Papillomavirus Infection Qiang Zhou • Kejian Zhu • Hao Cheng
Received: 18 April 2012 / Accepted: 13 February 2013 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2013
Abstract Infection with human papillomaviruses (HPVs) often causes cutaneous benign lesions, cervical cancer, and a number of other tumors. The mechanisms of host immune system to prevent and control HPV infection still remain poorly understood. Toll-like receptors (TLRs) are specific pattern recognition molecules that bind to microbial components to trigger innate immunity and direct adaptive immunity in the face of immunological danger. TLRs have been established to play an essential role in sensing and initiating antiviral immune responses. Recent accumulating evidence demonstrated that HPVs modulate TLR expression and interfere with TLR signaling pathways, leading to persistent viral infection and carcinogenesis. This review summarizes current knowledge on the roles of TLR during HPV infection, focusing on TLR recognition, modulation of TLR expression and signaling, regulatory receptors involved in TLR signaling, and cross-talk of TLRs with antimicrobial peptides. Immunotherapeutic strategies based on TLR agonists have emerged to be one of the novel promising avenues in treatment of HPV-associated diseases in the future. Keywords TLR HPV Innate immunity Adaptive immunity TLR agonist Abbreviations AP-1 Activator protein-1 AMPs Antimicrobial peptides BCR B cell receptor
Q. Zhou K. Zhu H. Cheng (&) Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 Qingchun Road East, Hangzhou 310016, People’s Republic of China e-mail: [email protected]
CA CIN DC DCIR FceR GAG hBD HPV IFN IKK IL IRAK IRF ITAM LC MAPKs mDC mdDC MyD88 NF-jB NK PAMPs pDC poly I:C RIP1 Siglec-H siRNA TAK1 TBK TIR TIRAP TLR
Condyloma acuminatum Cervical intraepithelial neoplasia Dendritic cell DC-immunoreceptor Fc receptor for IgE Glycosaminoglycan Human b-defensin Human papillomavirus Interferon IjB kinase kinase Interleukin IL-1 receptor-associated kinase IFN regulatory factor Immunoreceptor tyrosine-based activation motif Langerhans cell Mitogen-activated protein kinases Myeloid dendritic cell Monocyte-derived DC Myeloid-differentiation primary-response gene 88 Nuclear factor-kappa B Natural killer Pathogen-associated molecular patterns Plasmacytoid DC Polyinosinic-polycytidylic acid Receptor-interacting protein kinase 1 Sialic-acid-binding-immunoglobulin-like-lectin H Short interfering RNA TGF-b-activated kinase 1 Tank-binding kinase Toll/interleukin-1 receptor TIR domain-containing adaptor protein Toll-like receptor
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Arch. Immunol. Ther. Exp.
TRAM TRAF Treg TRIF VLPs
TRIF-related adaptor molecule Tumor necrosis factor receptor-associated factor Regulatory T cells TIR domain-containing adaptor protein inducing IFNb Virus-like particles
Introduction Human papillomaviruses (HPVs) are small double-stranded DNA viruses that comprise more than 130
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