Toll-like receptor 7-induced immune response to cutaneous West Nile virus infection.
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.
Welte
Thomas
T
Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Reagan
Krystle
K
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Fang
Hao
H
Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Machain-Williams
Carlos
C
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Zheng
Xin
X
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Mendell
Nicole
N
Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Chang
Gwong-Jen J
GJ
Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, 3150 Rampart Road, CDC-Foothills Campus, Fort Collins, CO 80521, USA.
Wu
Ping
P
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-0620, USA.
Blair
Carol D
CD
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Wang
Tian
T
Departments of Microbiology and Immunology, and Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
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*
D016207:Cytokines; D008562:Membrane Glycoproteins; D012367:RNA, Viral; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7