Table 1 Evidence for macrophage-driven pathogenesis and control of viral encephalitis
From: Inflammatory monocytes and the pathogenesis of viral encephalitis
Macrophage-derived mediators | Pathogenic and anti-viral functions in the central nervous system | Pathogenic role in mouse models | Anti-viral role in mouse models | |
|---|---|---|---|---|
Pro-inflammatory cytokines | IL-1β | ↑ pro-inflammatory cytokines | IL-1β−/− mice resistant to fatal neurovirulent Sindbis virus encephalitis [15] | IL-1β−/− mice exhibit increased mortality and virus loads in HSV-1 encephalitis [16] |
↑ leukocyte chemoattractants | ||||
IL-6 | ↑ adhesion molecules | IL-6−/− mice exhibit reduced seizures in TMEV encephalitis [17] |  | |
↑ NO/reactive oxygen species production | ||||
↑ neuronal misfiring/ seizures | ||||
↑ neuronal | ||||
↑ breakdown of BBB | ||||
↑ MMP | ||||
IL-12 | IL-12−/− mice show decreased clinical score during MHV encephalitis [23] | Infusion of IL-12 reduces viral loads and improves survival during vesicular stomatitis virus encephalitis [24] | ||
TNF | TNF-R−/− mice show improved survival in rabies virus encephalitis [25] | TNF−/− mice exhibit increased mortality and virus loads in HSV-1 encephalitis [16] | ||
Free radicals | NO/reactive oxygen species | ↑ neuronal misfiring/ seizures | Inhibition of NOS2 prolonged survival in rabies virus encephalitis by delaying virus replication and inhibiting of apoptosis [26] | NOS2−/− mice show increased susceptibility to CNS invasion and death in Murray Valley virus encephalitis [27] |
↑ neuronal damage/death | ||||
↑ formation of reactive oxygen species | ||||
Inhibition of NOS2 reduces mortality during Junin virus encephalitis [28] and neurovirulent Sindbis virus encephalitis [29] | ||||
Inhibition of NOS2 prolonged survival of WNV-infected animals [30] | ||||
Reviewed in [31] | ||||
Proteases | MMP | ↑ breakdown of the BBB | MMP-9−/− mice show reduced viral loads and increased survival during WNV encephalitis [32] |  |
↑ neuronal damage/death | ||||
↑ demyelination | ||||
↑ pro-inflammatory cytokines | ||||
Neurotransmitters | Glutamate | ↑ neuronal misfiring/seizures | Competitive and non-competitive glutamate receptor antagonists promote survival during neurovirulent Sindbis virus encephalitis [35, 36] and improved outcomes during coronavirus encephalitis [37] |  |
↑ neuronal damage/death | ||||
↑ production of NO/ROS | ||||
Reviewed in [38] | ||||