Table 1: Microglia activating agents.

Molecule/agentClassificationMechanism/actionReference

CpG-ODNTLR9 ligandIncreases microglia tumor infiltration and enhances the antigen-presenting capacity [8789]
poly (I:C)TLR3 ligandUnknown soluble factors [90]
IL-12Th1 cytokineIncreases tumor infiltration and enhances TRAIL and phagocytosis[91, 92]
TNFTh1 cytokineEnhances glioma cytotoxicity[93]
IFN- Th1 cytokineUpregulates class II MHC antigen expression[94]
Cytotoxic T cellsImmune cellsInduce microglia activation and recruitment[95, 96]
C1q, complement receptor 3 (CR3)ComplementMediates elimination of tagged synapses and activates microglia[97, 98]
T11TS/SLFA-3Glycopeptide Induces MHC class II expression and facilitates SLFA3/T11TS-CD2 immune activation[99, 100]
CeramideSphingolipidEnhances microglia production/secretion of brain-derived neurotrophic factor (BDNF)[101]
GangliosideGlycosphingolipidActivates microglia via protein kinase C and NADPH oxidase, which regulate activation of NF- B[102]
AdenosineNucleosideActs via A1 adenosine receptors in microglia[60]
Triggering receptor expressed on myeloid cells-2 (TREM2)Innate immune receptorIncreases phagocytosis[103]
ProthrombinBlood-clotting proteinActivates microglia via kringle-2 domain[104]
Propentofylline (PPF)MethylxanthineInhibits microglia migration toward tumor cells and decreases MMP-9 expression[105]
MinocyclineAntibioticReduces glioma expansion and invasion by attenuating microglia MT1-MMP expression[106]
Cyclosporin (CsA)ImmunosuppressantInhibits immunosuppressive microglia via MAPK signaling [107]
MifamurtideMuramyl dipeptideEnhances macrophage cytotoxicity and has been used for osteosarcoma treatment [108]
ButyrateFatty acidAnti-inflammatory in primary, brain-derived microglia cells, but is proinflammatory in transformed, proliferating N9 microglia[109]
I-125Radioactive isotopeStimulates microglia/macrophage to remove necrotic debris[110]