Mice naturally resistant to Yersinia pestis Delta pgm strains commonly used in pathogenicity studies

Abstract

We report that females of some substrains of inbred mouse strain 129 are resistant to systemic plague due to conditionally virulent Deltapgm strains of Yersinia pestis; however, fully virulent Y. pestis is not attenuated in these mice. Therefore, these mice offer a powerful system in which to map in parallel host resistance traits and opposing bacterial virulence properties for plague.

FIG. 1.

Robust acute inflammation was under way late in infection of resistant female 129 mice with Y. pestis KIM5. Sections from formalin-fixed livers of infected female 129S2/P2 (Gca^−/−) mice (left panel), noninfected female 129S2/P2 (Gca^−/−) mice (middle panel), or infected female C57BL/6 mice (right panel) were stained with hematoxylin and eosin, and representative fields for day 4 postinfection are shown. The bacterial dose given to the 129S2/P2 (Gca^−/−) mice was 7.7 × 10³ CFU; the dose for the susceptible female C57BL/6 mice was 10² CFU.

FIG. 2.

Infection of female 129 mice caused an influx of macrophages, PMNs, and NK cells into the spleen. Leukocyte populations in the spleen were analyzed by flow cytometry for the percentages of macrophages, CD4⁺ T cells, CD8⁺ T cells, PMNs, and NK cells in mice infected with Y. pestis KIM5 (open bars) or the YopM⁻ strain (closed bars) on day four postinfection. The data represent the average results ± standard deviations (error bars) from three infected mice; data for noninfected mice are provided for reference (hatched bars). The values for macrophages, PMNs, and NK cells for mice infected with both Y. pestis KIM5 and the YopM⁻ strain differed significantly from those for noninfected mice by the unpaired t test (n = 3), with two-tailed P values of 0.011, 0.0026, and 0.034 for the three mice infected with Y. pestis KIM5 and 0.017, 0.018, and 0.0038 for the three mice infected with the YopM⁻ strain. The same statistical test found no significant difference between the values for Y. pestis KIM5 and the YopM⁻ mutant for macrophages, PMNs, NK cells, or CD8⁺ T cells. The difference in values for CD4⁺ T cells in mice infected with the parent and mutant strains was statistically significant but was not always observed.