Fig 1.
Survival of M. tuberculosis-infected mice. We infected 8- to 10-week-old, female Diversity Outbred (DO) mice and C57BL/6J mice with aerosolized M. tuberculosis bacilli and monitored as described in Materials and Methods. Non-infected, identically housed, and age- and gender-matched Diversity Outbred mice served as controls. Mice were euthanized at a predetermined timepoint, or if any one of three morbidity criteria developed a body condition score of <2, severe lethargy, or increased respiratory rate/effort. (A) The percent alive over time (cumulative survival) and the red vertical line mark 60 days post-infection when approximately 30% of Diversity Outbred mice succumbed to pulmonary TB due to early morbidity (progressors). Controllers survived at least 60 days without morbidity and succumbed later. Survival of non-infected Diversity Outbred mice (brown dashed line), infected Diversity Outbred (brown solid line), and infected inbred C57BL/6J (solid gray line) mice was significantly different by Mantel-Cox log-rank test. ****P < 0.0001. (B) A subset of 556 mice from panel A that were euthanized because of pulmonary TB-related morbidity (526 mice) or non-infected controls euthanized at the end of the experiment (30 mice). Groups are shown on the X-axis box-and-whiskers plots in panel B, with interquartile range with whiskers at the minimum and maximum. Statistical analysis was performed using Brown-Forsythe and Welch’s one-way analysis of variance followed by Dunnett’s T3 post-test. ****P < 0.0001.