Toll-like receptor (TLR) 2-9 agonists-induced Cytokines & Chemokines: I. Comparison with T cell receptor-induced responses.

Ghosh, T.K., Michelson, D.J., Fink, J., Solberg, J.C., Inglefield, J.R., Hook, D., Gupta, S.K., Gibson, S., Alkan, S.S.

Journal	Cell Immunol.	Year	2006
Species	Human	Volume	243 (1)
Analytes Measured	IFN-α, IFN-β, IFN-γ, IL-1β, IL-10, IL-12 p40, IL-12 p70, IL-13, IL-2, IL-4, IL-8, MCP-1, MIP-1β, RANTES, TNF-α	Page #	48-57
Matrix Tested	Peripheral blood mononuclear cell (PBMC) culture supernatants	Category	Cytokines & Chemokines

Abstract

The cells of innate and adaptive immunity, although activated by different ligands, engage in cross talk to ensure a successful immune outcome. To better understand this interaction, we examined the demographic picture of individual TLR (TLRs 2-9) -driven profiles of eleven cytokines (IFN-alpha/beta, IFN-gamma, IL-12p40/IL-12p70, IL-4, 1L-13, TNF-alpha, IL-1beta, IL-2, IL-10) and four chemokines (MCP-1, MIP1beta, IL-8, and RANTES), and compared them with direct T-cell receptor triggered responses in an assay platform using human PBMCs. We find that T-cell activation by a combination of anti-CD3/anti-CD28/PHA induced a dominant IL-2, IL-13, and Type-II interferon (IFN-gamma) response without major IL-12 and little Type-I interferon (IFN-alphabeta) release. In contrast, TLR7 and TLR9 agonists induced high levels of Type-I interferons. The highest IFN-gamma levels were displayed by TLR8 and TLR7/8 agonists, which also induced the highest levels of pro-inflammatory cytokines IL-12, TNF-alpha, and IL-1beta. Amongst endosomal TLRs, TLR7 displayed a unique profile producing weak IL-12, IFN-gamma, TNF-alpha, IL-1beta, and IL-8. TLR7 and TLR9 resembled each other in their cytokine profile but differed in MIP-1beta and MCP1 chemokine profiles. Gram positive (TLR2, TLR2/6) and gram negative (TLR4) pathogen-derived TLR agonists displayed significant similarities in profile, but not in potency. TLR5 and TLR2/6 agonists paralleled TLR2 and TLR4 in generating pro-inflammatory chemokines MCP-1, MIP-1beta, RANTES, and IL-8 but yielded weak TNF-alpha and IL-1 responses. Taken together, the data show that diverse TLR agonists, despite their operation through common pathways induce distinct cytokine/chemokine profiles that in turn have little or no overlap with TCR-mediated response.