Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice.
Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. Our results revealed that IFN-gamma is redundant in the afferent phase of the antiviral T cell response as well as a local mediator of this T cell mediated inflammatory disease. However, IFN-gamma may play an indirect role as it is involved in reducing extraneural infection that may compete with CNS for available effector cells. Analysis of the inflammatory exudate disclosed that leucocyte recruitment was unimpaired in the absence of IFN-gamma as was the upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site. However, local macrophage activation (production of tumor necrosis-alpha and NO) was significantly impaired. Notably, a viral peptide could also elicit a T cell mediated inflammatory response in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to inflammatory reactions triggered by an active infection. Thus, T cell mediated inflammation may be induced in the absence of IFN-gamma and local macrophage activation.
Nansen
A
A
Institute of Medical Microbiology and Immunology, Panum Institute, Copenhagen N, Denmark.
Christensen
J P
JP
Röpke
C
C
Marker
O
O
Scheynius
A
A
Thomsen
A R
AR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D004487:Edema / Q000276:immunology / Q000821:virology; D004727:Endothelium / Q000737:chemistry / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000235:genetics*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000472:pathogenicity; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008578:Meninges / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014774:Virulence
D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma