TLR adjuvants mediate distinct innate responses in both peripheral blood and draining LNs
| . | MPL TLR4-L . | R-848 TLR7/8-L . | CpG-ODN TLR9-L . |
|---|---|---|---|
| Peripheral blood | |||
| Cellular response* | ↑↑ Neutrophils | ↑↑↑ Neutrophils | ↑↑ Neutrophils |
| ↑↑↑ CD14+CD16− monocytes | ↑↑↑ CD14+CD16+ monocytes | ↑↑ CD14+CD16+ monocytes | |
| ↑↑↑ activation of pDCs and mDCs | ↑↑ expansion/activation of pDCs | ||
| Serum cytokines† | ↑ IL-6, IL-1ra | ↑↑↑ IFN-α, IP-10, IL-6, IL-1ra, IFN-γ | ↑↑ IFN-α, IP-10 |
| ↑ IL-6, IL-1ra | |||
| Gene signatures‡ | ↑↑ Edn-1 | ↑↑↑ ISGs, chemokines, cytokines (3-24 h) | ↑↑ ISGs, chemokines, cytokines, adhesion (3 h-6 d) |
| Draining LNs | |||
| Cellular response* | ↑↑ CD14+CD16− monocytes (day 3) | ↑ Activation of CD14+CD16+ (day 1) | ↑↑↑ Expansion/activation of CD14+CD16+ monocytes (days 1-3) |
| ↑↑ mDCs (day 3) | ↑ Activation of mDCs and pDCs (day 1) | ↑↑↑ Expansion of pDCs (days 1-3) | |
| Gene signatures‡ | ↑ Complement, adhesion (day 3) | ↑ ISGs, chemokines (day 1) | ↑↑↑ ISGs, chemokines, complement (days 1-3) |
| . | MPL TLR4-L . | R-848 TLR7/8-L . | CpG-ODN TLR9-L . |
|---|---|---|---|
| Peripheral blood | |||
| Cellular response* | ↑↑ Neutrophils | ↑↑↑ Neutrophils | ↑↑ Neutrophils |
| ↑↑↑ CD14+CD16− monocytes | ↑↑↑ CD14+CD16+ monocytes | ↑↑ CD14+CD16+ monocytes | |
| ↑↑↑ activation of pDCs and mDCs | ↑↑ expansion/activation of pDCs | ||
| Serum cytokines† | ↑ IL-6, IL-1ra | ↑↑↑ IFN-α, IP-10, IL-6, IL-1ra, IFN-γ | ↑↑ IFN-α, IP-10 |
| ↑ IL-6, IL-1ra | |||
| Gene signatures‡ | ↑↑ Edn-1 | ↑↑↑ ISGs, chemokines, cytokines (3-24 h) | ↑↑ ISGs, chemokines, cytokines, adhesion (3 h-6 d) |
| Draining LNs | |||
| Cellular response* | ↑↑ CD14+CD16− monocytes (day 3) | ↑ Activation of CD14+CD16+ (day 1) | ↑↑↑ Expansion/activation of CD14+CD16+ monocytes (days 1-3) |
| ↑↑ mDCs (day 3) | ↑ Activation of mDCs and pDCs (day 1) | ↑↑↑ Expansion of pDCs (days 1-3) | |
| Gene signatures‡ | ↑ Complement, adhesion (day 3) | ↑ ISGs, chemokines (day 1) | ↑↑↑ ISGs, chemokines, complement (days 1-3) |
Expansion of cell numbers and activation were assessed by flow cytometry in freshly isolated PBMCs or LNs.
Serum cytokines were measured in plasma samples by Luminex (IL-6, IFN-γ, and IL-1ra) or ELISA (IFN-α and IP-10).
Gene expression in PBMCs and LNs was assessed by a custom-designed low-density array and quantitative real-time PCR.