|
Before ART
|
• Paucity of appropriate inflammation for cryptococcosis and/or |
• ↓ TNF-α, G-CSF, GM-CSF, VEGF in serum↓ IFN-γ, G-CSF, TNF-α, IL-6 in CSF [46]
|
|
• Inappropriate (Th2) responses resulting in: |
• ↑IL-4 pre-ART |
|
• Poor antigen clearance, pre-ART |
• Similar CSF CRAG at initial infection [46]Higher CRAG pre-ART |
|
After starting ART
|
• Increasing proinflammatory signaling from APCs due to persisting antigen burden and failure to clear antigen |
• ↑ IL6 from macrophages [56] then downstream ↑ CRP production; ↑ IL-7 from APCs |
|
• Secondary activation of coagulation cascade |
• ↑ D-dimer |
|
At IRIS
|
• Cytokine storm of multiple immune pathways of innate and adaptive immune systems |
• Th1 ↑ INF-γ, VEGF; TH17 ↑ IL-17Innate: ↑ IL-8, G-CSF, GM-CSF |
|
• Activation of coagulation cascade |
• ↑ D-dimer |
|
• Neuronal cell activation and damage |
• ↑ FGF-2 |
