Figure 4. TNFα and IFNγ contribute to protection mediated by sub-optimal doses of mAb specific for F1 or LcrV.

Wild-type C57BL/6 mice were infected intranasally with Y. pestis (10 LD-50; 2×10⁵ CFU). (A) The following day, they were left untreated or were treated with a sub-optimal dose of F1-specific mAb (0.3 μg; open circles) or that dose of F1-specific mAb along with neutralizing mAb specific for TNFα and IFNγ (anti-TNF/IFN; closed triangles). All untreated mice succumbed by day 9 (not shown). In comparison with mice treated with F1-specific mAb alone, the mice treated with F1-specific mAb along with cytokine-neutralizing mAb exhibited significantly reduced survival (p = 0.0002; n = 15 mice per group). Data are pooled from three independent experiments. (B) In parallel with (A), additional groups of mice were treated with a sub-optimal dose of LcrV-specific mAb (1 μg; open circles) or that dose of LcrV-specific mAb along with neutralizing mAb specific for TNFα and IFNγ (closed triangles). In comparison with mice treated with LcrV-specific mAb alone, the mice treated with LcrV-specific mAb along with cytokine-neutralizing mAb exhibited significantly reduced survival (p = 0.001; n = 15 mice per group). Data are pooled from three independent experiments. (C) In parallel with (A) and (B), groups of mice were euthanized on day 4 after initiating infection and bacterial burden was measured. In comparison with mice treated with F1- or LcrV-specific mAb alone (open circles), mice treated with F1- or LcrV-specific mAb along with cytokine-neutralizing mAb (closed triangles) exhibited significantly increased bacterial burden in lung and liver (* p < 0.05 by ANOVA with Bonferroni’s post test; n = 4–5 mice per group). The bars depict the means and the dashed line depicts the limit of detection. Similar results were observed on day 3 after initiating infection in a second, independent, experiment.