Generation of a protective T-cell response following coronavirus infection of the central nervous system is not dependent on IL-12/23 signaling.

Abstract

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.

• Authors: Katherine S Held, William G Glass, Yevgeniya I Orlovsky, Kimberly A Shamberger, Ted D Petley, Patrick J Branigan, Jill M Carton, Heena S Beck, Mark R Cunningham, Jacqueline M Benson, Thomas E Lane
• Journal: Viral immunology (Viral Immunol) Vol. 21 Issue 2 Pg. 173-88 (Jun 2008) ISSN: 0882-8245 [Print] United States
• PMID: 18570589 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-23
• Interleukin-12

Topics

• Animals
• Autoimmune Diseases
• Central Nervous System (immunology, pathology)
• Coronavirus Infections (immunology, pathology)
• Demyelinating Diseases (immunology)
• Encephalomyelitis (immunology)
• Female
• Interleukin-12 (immunology)
• Interleukin-23 (immunology)
• Mice
• Murine hepatitis virus (immunology)
• T-Lymphocytes (immunology)