Figure 1.
Lung viral and bacterial titers from mice infected with influenza A virus then infected 7 days later with pneumococcus.
In the first set of experiments (Panels A and B), mice were infected with of influenza A virus PR8 then 7 days later with either S. pneumoniae strain D39 (100 CFU or 1000 CFU) or A66.1 (1000 CFU). Panels C and D show comparable experiments in which mice were infected with
of influenza A virus PR8-PB1-F2(1918) then 7 days later with D39 (1000 CFU). Control experiments in which mice were infected with only virus or only bacteria are also shown. Data are given as geometric means
SD.
Figure 2.
Dichotomy of bacterial lung titers.
Individual (black dots) and average (colored boxes/triangles) values of bacterial titers to illustrate the generation of high or low titers that can occur in some infections. Mice were infected with either (A)
PR8 virus followed 7 days later by 100 CFU S. pneumoniae strain D39 or (B)
PR8-PB1-F2(1918) virus followed 7 days later by 1000 CFU S. pneumoniae strain D39.
Figure 3.
Schematic diagram of the coinfection model dynamics.
Dashed lines indicate the interactions between influenza and pneumococcus, including (i) increased bacterial adherence to infected cells, (ii) increased infected cell death from bacterial adherence, (iii) viral-induced decrease in phagocytosis of bacteria, and (iv) bacterial-induced increase in virus release.
Figure 4.
Coinfection model fit to lung titers of mice coinfected with PR8 and 1000 CFU D39.
Fit of the coinfection model (Equations (6)–(10)) to viral (panel A) and bacterial (panel B) lung titers from individual mice infected with PR8 virus followed 7 days later by 1000 CFU S. pneumoniae strain D39. Parameters for the model curves are in Tables 1–2.
Table 1.
Previously established parameter values of the influenza model (Equations (1)–(4)) [41] and the pneumococcus model (Equation (5)) [8].
Table 2.
Parameter estimates and 95% confidence intervals from the coinfection model (Equations (6)–(10)) for the dynamics of infection with 1000 CFU D39 7 days after PR8 or PR8-PB1-F2(1918) infection.
Figure 5.
Simulation of the coinfection model with lung titers of mice coinfected with PR8 and 100 CFU D39.
Numerical simulation of the coinfection model, Equations (6)–(10) with parameter values in Tables 1–2 against lung titers from individual mice infected with PR8 virus (panel A) followed 7 days later by 100 CFU S. pneumoniae strain D39 (panel B).
Figure 6.
Coinfection model fit to lung titers of mice coinfected with PR8-PB1-F2(1918) and 1000 CFU D39.
Fit of the coinfection model (Equations (6)–(10)) to viral (panel A) and bacterial (panel B) lung titers from individual mice infected with PR8-PB1-F2(1918) virus followed 7 days later by 1000 CFU S. pneumoniae strain D39. Parameters for the model curves are in Tables 1–2.
Table 3.
Summary of the coinfection model hypotheses, results and possible experiments to confirm each hypothesis.