Early Systemic Bacterial Dissemination And A Rapid Innate Immune Response Characterize Genetic Resistance To Plague Of Seg Mice

Background. Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance.Methods. The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92.Results. Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1a, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis.Conclusion. A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague.