Enhanced viral immunoinflammatory lesions in mice lacking IL-23 responses.
Herpes simplex virus (HSV) infection of the cornea culminates in an immunopathological lesion (stromal keratitis--SK) that impairs vision. This report shows that HSV infection results in IL-23 up-regulation, but if this response fails to occur, as was noted in p19-/- mice, the severity of lesions, their incidence and the level of viral induced angiogenesis were significantly increased compared to wild-type (WT) animals (p<0.05). The higher disease severity in p19-/- mice appeared to be the consequence of an increased IL-12 response that in turn led to the induction of higher numbers of IFN-gamma producing CD4(+)T cells, the principal orchestrators of SK. Our results indicate that the severity of HSV induced immunopathological lesions may be mainly the consequence of IL-12 driven Th1 T cell reactions rather than the action of IL-17 producing cells controlled by IL-23.
Kim
Bumseok
B
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Sarangi
Pranita P
PP
Azkur
Ahmet Kursat
AK
Kaistha
Shilpa Deshpande
SD
Rouse
Barry T
BT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D003315:Cornea / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity / Q000502:physiology*; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000737:chemistry / Q000378:metabolism*; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008970:Molecular Weight; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000276:immunology; D014774:Virulence; D014779:Virus Replication
D053759:Interleukin-23; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma