Fig 1.
Enhanced susceptibility of Myd88-/- mice for D39 or D39Δcps.
(A) Bacterial loads in lung homogenates of wild type mice (WT, black bars) and Myd88-/- mice (MyD88 KO, white bars) at 6 and 48 hours after infection with 5x106 CFU S. pneumoniae D39, and (B), 6 and 24 hours after infection with 1x108 CFU D39Δcps. BC+ indicates the number of positive blood cultures. Data are mean ± SEM. (N = 6–8 mice per group at each time point). *P<0.05, **P<0.005, ***P<0.0005 vs WT mice.
Fig 2.
Lung pathology in WT and Myd88-/- mice during infection with capsulated and unencapsulated D39.
Representative lung sections obtained 6 or 48 h after induction of pneumococcal pneumonia with D39 in WT (A and D) and Myd88-/- mice (B and E) and 6 or 24 h after inoculation with D39Δcps in WT mice (G and J) and MyD88-/- mice (H and K). Haematoxylin and eosin stainings show different levels of inflammation. Original magnification 20x. Findings were quantified by histology scoring, as described in methods section for wild type (WT, black bars) and Myd88-/- mice (MyD88 KO, white bars). Data are mean ± SEM (N = 5–8 mice per group at each time point). **P<0.005 vs WT mice.
Fig 3.
Reduced neutrophil infiltration in the lung in Myd88 -/- mice during infection with D39 or D39Δcps.
Representative Ly6-C/G stainings of lung sections obtained 6 h after induction of pneumococcal pneumonia with D39 in WT and Myd88-/- mice (A and B) and with D39Δcps in WT mice and Myd88-/- mice (E and F). Original magnification 20x. Percentage lung area with Ly6-C/G-positive neutrophils was quantified by digital image analysis as described in methods section for wild type (WT, black bars) and Myd88-/- mice (MyD88 KO, white bars)(C and G). Levels of MPO in lung homogenates of wild type (WT, black bars) and Myd88-/- mice (MyD88 KO, white bars) inoculated with D39 at 6 and 48 hours after challenge, or inoculated with D39Δcps (D and H) at 6 and 24 hours after challenge were determined by ELISA. Data are mean ± SEM (N = 5–8 mice per group at each time point). *P<0.05, ***P<0.0005 vs WT mice.
Fig 4.
Reduced cytokine production in the lung of Myd88-/- mice during infection with D39 or D39Δcps.
Lung levels of TNF-α (A and B), IL-1β (C and D) and IL-6 (E and F) of wild type (WT, black bars) and Myd88-/- mice (MyD88 KO, white bars) at 6 and 48 hours after inoculation with D39 (A/C/E) or at 6 or 24 hours post inoculation of D39Δcps (B/D/F). Data are mean ± SEM (N = 6–8 mice per group at each time point). *P<0.05, **P<0.005, ***P<0.0005 vs WT mice.
Fig 5.
Reduced chemokine production in the lung of Myd88-/- mice during infection with D39 or D39Δcps.
KC/CXCL1 (A and B) and MIP2/CCL2 (C and D) of wild type (WT, black bars) and Myd88-/- mice (MyD88 KO, white bars) at the indicated time points after inoculation with D39 (A/C) or at 6 or 24 hours post inoculation D39Δcps (B/D). Data are mean ± SEM (N = 6–8 mice per group at each time point). ***P<0.0005 vs WT mice.