TLR Cross-talk Confers Specificity to Innate Immunity

Figures & data

TABLE 1.  A summary of TLR-TLR crosstalk resulting in cytokine synergy.

Cell type	Derivation	Combinations	Cytokine	Mechanism	Refs
Dendritic cells
Human moDC	CD14 selection, GM-CSF, IL-4	TLR3/4 and TLR8	IL-12p70	Sustained c-Jun	[36]
Human moDC	CD14 selection, GM-SCF, IL-4	TLR4 and TLR8	IL-12p70, IL-6, IL-10, TNF	p38	[55]
Human moDC	CD14 selection, GM-SCF, IL-4	TLR3 and TLR2/6/5	IL-12p70	Not studied	[55]
Human moDC	Negative selection, GM-CSF, IL-4	TLR3/4 and TLR8	IL-12p70, IL-6, IL-10, TNF	p38, NF-κB, PI3K	[56]
Mouse BM-DC	GM-CSF	TLR3 and TLR9	IL-12p70	Autocrine type I IFN	[48]
Mouse BM-DC	Negative selection, GM-CSF, TNF	TLR3/4 and TLR8	IL-12p70	Type I IFN loop	[46]
Mouse BM-DC	Negative selection, GM-CSF	TLR2 and TLR4	IL-10	p38, JNK	[57]
Mouse BM-DC	GM-CSF	TLR2, TLR3 and TLR9	IL-12p70 and IL-15	Not studied	[38]
Macrophages
Human moMϕ	Adherence, GM-CSF	TLR3/4 and TLR8	No synergy	Not studied	[56]
Mouse BM-DM	Teflon adherence	TLR3/4 and TLR2/5/9	TNF, IL-6	NF-κB, not IFN-β	[43]
Mouse BM-DM	M-CSF	TLR4 and TLR9	TNF, IL-6	JNK	[34]
PEC	Thioglycollate-induced	TLR3/4 and TLR7/9	IL-12p40	IRF5	[44]

This table compares the various studies investigating cytokine synergy in TLR-TLR stimulation, based on the cell type studied, derivation method, combination of TLR ligands, cytokines shown to be synergistically regulated, proposed mechanisms, and the respective references. moDC, monocyte-derived dendritic cells. BM-DM, bone marrow-derived macrophages. moMϕ, monocyte-derived macrophages. PEC, peritoneal exudate cells. GM-CSF, granulocyte-macrophage colony stimulating factor. M-CSF, macrophage colony stimulating factor.

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