Generation of a protective T-cell response following coronavirus infection of the central nervous system is not dependent on IL-12/23 signaling.
The functional role of IL-12 and IL-23 in host defense and disease following viral infection of the CNS was determined. Instillation of mouse hepatitis virus (MHV, a positive-strand RNA virus) into the CNS of mice results in acute encephalitis followed by a chronic immune-mediated demyelinating disease. Antibody-mediated blocking of either IL-23 (anti-IL-23p19) or IL-12 and IL-23 (anti-IL-12/23p40) signaling did not mute T-cell trafficking into the CNS or antiviral effector responses and mice were able to control viral replication within the brain. Therapeutic administration of either anti-IL-23p19 or anti-IL-12/23p40 to mice with viral-induced demyelination did not attenuate T-cell or macrophage infiltration into the CNS nor improve clinical disease or diminish white matter damage. In contrast, treatment of mice with anti-IL-12/23p40 or anti-IL-23p19 resulted in inhibition of the autoimmune model of demyelination, experimental autoimmune encephalomyelitis (EAE). These data indicate that (1) IL-12 and IL-23 signaling are dispensable in generating a protective T-cell response following CNS infection with MHV, and (2) IL-12 and IL-23 do not contribute to demyelination in a model independent of autoimmune T-cell-mediated pathology. Therefore, therapeutic targeting of IL-12 and/or IL-23 for the treatment of autoimmune diseases may offer unique advantages by reducing disease severity without muting protective responses following viral infection.
Held
Katherine S
KS
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA.
Glass
William G
WG
Orlovsky
Yevgeniya I
YI
Shamberger
Kimberly A
KA
Petley
Ted D
TD
Branigan
Patrick J
PJ
Carton
Jill M
JM
Beck
Heena S
HS
Cunningham
Mark R
MR
Benson
Jacqueline M
JM
Lane
Thomas E
TE
D000818:Animals; D001327:Autoimmune Diseases; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology; D003711:Demyelinating Diseases / Q000276:immunology; D004679:Encephalomyelitis / Q000276:immunology; D005260:Female; D018664:Interleukin-12 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D051379:Mice; D006517:Murine hepatitis virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D053759:Interleukin-23; D018664:Interleukin-12