Figure 1.
Synergistic TLR stimulation protects against lethal influenza pneumonia, while individual TLR ligands confer no protection.
Swiss-Webster mice were challenged with influenza A/Hong Kong/8/68 (H3N2) 24 h after aerosolized treatment with PBS (sham), Pam2, ODN or both (Pam2-ODN). Shown are survival (A) and body weight (B) of the mice through day 22 after infection (mean ± s.d.). (n = 20 mice/group; *p = 0.03 vs. PBS treated).
Figure 2.
Synergistic TLR stimulation protects against influenza pneumonia whether given before or after infection.
Mice were challenged with influenza A following a single aerosolized treatment with Pam2-ODN 3 d before infection, 1 d before infection or 1 d after infection or following a single aerosol treatment with PBS 1 d before infection. Shown are survival (A) and body weight (B) of the mice through day 22 after infection (mean ± s.d.). Log viral titer of lung homogenates is shown for day 4 after infection for the same groups (C, mean ± s.d.). (n = 20 mice group for survival and weight, n – 5 mice/group for lung titers; * p<0.0001 vs. PBS treated, ** p<0.002 vs. PBS treated, † p<0.05 vs. PBS treated).
Figure 3.
Synergistic TLR2/6 and TLR9 protects against influenza with or without TLR3 stimulation.
Mice were challenged with influenza 1 day after a single inhaled treatment with the described treatments. Shown are survival (A) and body weight (B) of mice through 22 days after challenge (mean ± s.d.). “2x” indicates doubling of the concentration of all TLR ligand components in a corresponding “1x” treatment. (n = 20 mice/group; * p<0.00001 vs. PBS treated, ** p<0.02 vs. PBS treated, † p<0.0001 vs. poly(I∶C) treated, †† p = 0.002 vs. poly(I∶C) treated, # p = 0.004 vs. poly(I∶C) treated).
Table 1.
Interferon responses to Pam2-ODN.
Table 2.
Inflammatory cytokine responses to Pam2-ODN.
Figure 4.
Pam2 treatment synergizes with all classes of TLR9-stimulating CpG oligodeoxynucleotides.
Mice were challenged with influenza 1 day after a single inhaled treatment with the described treatments. Shown are survival (A) and body weight (B) of mice through 22 days after challenge (mean ± s.d.). (n = 20 mice/group; * p<0.00001 vs. PBS treated, ** p = 0.0004 vs. PBS treated, † p = 0.01 vs. Pam2+ODN 2006 treated, † p = 0.1 vs Pam2+ODN 2006 treated).
Figure 5.
Synergistic TLR stimulation protects against swine-origin H1N1 influenza A pneumonia.
Mice were challenged with influenza 1 day after a single inhaled treatment with Pam2 and ODN. Shown are survival (A) and body weight (B) of mice through 22 days after challenge (mean ± s.d.). (n = 20 mice/group; * p = 0.0004 vs. PBS treated).