title: Toll-like receptor 7-induced immune response to cutaneous West Nile virus infection.
abstract: The Toll-like receptor (TLR) 7 response represents a vital host-defence mechanism in a murine model of systemic West Nile virus (WNV) infection. Here, we investigated the role of the TLR7-induced immune response following cutaneous WNV infection. We found that there was no difference in susceptibility to WNV encephalitis between wild-type and TLR7(-/-) mice upon intradermal injection or infected mosquito feeding. Viral load analysis revealed similar levels of WNV RNA in the peripheral tissues and brains of these two groups of mice following intradermal infection. There was a higher level of cytokines in the blood of wild-type mice at early stages of infection; however, this difference was diminished in the blood and brains at later stages. Langerhans cells (LCs) are permissive to WNV infection and migrate from the skin to draining lymph nodes upon intradermal challenge. Our data showed that WNV infection of TLR7(-/-) keratinocytes was significantly higher than that of wild-type keratinocytes. Infection of wild-type keratinocytes induced higher levels of alpha interferon and interleukin-1beta (IL-1beta), IL-6 and IL-12, which might promote LC migration from the skin. Co-culture of naïve LCs of wild-type mice with WNV-infected wild-type keratinocytes resulted in the production of more IL-6 and IL-12 than with TLR7(-/-) keratinocytes or by cultured LCs alone. Moreover, LCs in the epidermis were reduced in wild-type mice, but not in TLR7(-/-) mice, following intradermal WNV infection. Overall, our results suggest that the TLR7 response following cutaneous infection promotes LC migration from the skin, which might compromise its protective effect in systemic infection.
authors.affiliation: Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Krystle
authors.initials: K
authors.lastname: Reagan
authors.affiliation: Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Machain-Williams
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mendell
authors.affiliation: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, 3150 Rampart Road, CDC-Foothills Campus, Fort Collins, CO 80521, USA.
authors.forename: Gwong-Jen J
authors.initials: GJ
authors.lastname: Chang
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-0620, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
authors.affiliation: Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis / Q000097:blood; D005260:Female; D015603:Keratinocytes / Q000821:virology; D007801:Langerhans Cells / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012367:RNA, Viral / Q000097:blood; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000276:immunology*; D019562:Viral Load; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D012367:RNA, Viral; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7