Innate recognition network driving herpes simplex virus-induced corneal immunopathology: role of the toll pathway in early inflammatory events in stromal keratitis.
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.
Department of Microbiology, The University of Tennessee, M409 Walters Life Sciences Bldg., 1414 Cumberland Avenue, Knoxville, TN 37996, USA.
Pranita P
PP
Sarangi
Bumseok
B
Kim
Evelyn
E
Kurt-Jones
Barry T
BT
Rouse
D000818:Animals; D003319:Corneal Stroma / Q000821:virology*; D004198:Disease Susceptibility; D007249:Inflammation / Q000276:immunology; D007634:Keratitis / Q000209:etiology / Q000276:immunology / Q000821:virology*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D018139:Simplexvirus / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9