Neuroimmunology of central nervous system viral infections: the cells, molecules and mechanisms involved.
Viral infections of the central nervous system (CNS) necessitate rapid, yet tightly controlled responses to contain viral spread while limiting tissue damage. All CNS resident cell types are equipped with pattern recognition receptors (PRRs) to respond to viruses. The resulting activation of IFN-alpha/beta, pro-inflammatory cytokines and chemokines is dependent on the virus replication strategy, tropism and PRR distribution. Although IFN-alpha/beta induced antiviral mediators are essential to restrict initial viral spread, adaptive immunity promoted by chemokines, cytokines and metalloproteinases is equally crucial in lowering viral burden. Recognition of viral antigen presented by MHC molecules is crucial for T cell retention and function. Non-lytic clearance mechanisms mediated by IFN-gamma and antibodies prevail in providing protection. Targeted intervention can be achieved by PRR stimulation, chemokine-receptor blockade and immune modulation of T cell function. However, owing to the extensive positive and negative feedback signaling cascades linking innate and adaptive immune responses, enhanced anti-viral functions will have to be counterbalanced to avoid pathology.
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. savaric@ccf.org
Carine
C
Savarin
Cornelia C
CC
Bergmann
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D018925:Chemokines / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000502:physiology*; D007155:Immunologic Factors / Q000235:genetics / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology; D007372:Interferons / Q000276:immunology / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology; D051192:Receptors, Pattern Recognition / Q000502:physiology
D000998:Antiviral Agents; D018925:Chemokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D019707:Receptors, Chemokine; D051192:Receptors, Pattern Recognition; D007372:Interferons