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Journal of Virology, October 2007, p. 11128-11138, Vol. 81, No. 20
0022-538X/07/$08.00+0 doi:10.1128/JVI.01008-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Innate Recognition Network Driving Herpes Simplex Virus-Induced Corneal Immunopathology: Role of the Toll Pathway in Early Inflammatory Events in Stromal Keratitis
Pranita P. Sarangi,1
Bumseok Kim,2
Evelyn Kurt-Jones,3 and
Barry T. Rouse1*
Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 37996-0845,1
Biosafety Research Institute and Department of Pathology, College of Veterinary Medicine, Chonbuk National University, Chonju, South Korea,2
Department of Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts3
Received 9 May 2007/
Accepted 26 July 2007
Ocular infection with herpes simplex virus (HSV) sets off an array of events that succeed in clearing virus from the cornea but leaves the tissue with a CD4+ T-cell-orchestrated chronic inflammatory lesion that impairs vision. We demonstrate that Toll-like receptor (TLR) signaling forms a part of the recognition system that induces the syndrome that eventually culminates in immunopathology. Accordingly, in a comparison of the outcomes of infection in wild-type (WT) mice and those lacking TLR function, it was apparent that the absence of TLR2 and, to a lesser extent, TLR9 resulted in significantly diminished lesions. Similarly, mice lacking the adapter molecule MyD88 were resistant to lesion development, but such animals were also unable to control infection, with most succumbing to lethal encephalitis. The susceptibility of TLR4–/– animals was also evaluated. These animals developed lesions, which were more severe, more rapidly than did WT animals. We discuss the possible mechanisms by which early recognition of HSV constituents impacts the subsequent development of immunopathological lesions.
* Corresponding author. Mailing address: Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Bldg., 1414 Cumberland Avenue, Knoxville TN 37996. Phone: (865) 974-4026. Fax: (865) 974-7817. E-mail:
btr{at}utk.edu
Published ahead of print on 8 August 2007.
Journal of Virology, October 2007, p. 11128-11138, Vol. 81, No. 20
0022-538X/07/$08.00+0 doi:10.1128/JVI.01008-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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