Yersinia pestis elicits growth‐condition dependent patterns of dendritic cell IL12p40 production and CCL19‐dependent chemotaxis

Yersinia pestis is the causative agent of bubonic plague. At the temperature of Y. pestis natural flea vector (26°C), Y. pestis expresses a profile of genes and lipopolysaccharide variants that are distinct from those expressed in a mammalian host (37°C). As dendritic cells (DCs) are targeted by Y. pestis, we examined whether DC production of IL‐12p40 ‐ a critical component of both cellular and humoral immunity ‐ was differentially stimulated by Y. pestis grown at 26°C versus Y. pestis grown at 37°C (hereafter referred to as Y.pestis‐26° and Y. pestis‐37°, respectively). Using IL12p40‐reporter bone‐marrow derived DCs (BMDCs) we demonstrate that Y.pestis‐26° is capable of eliciting a >25‐fold increase in IL12p40 production above unstimulated controls in a dose‐dependent manner. This IL12p40 response, however, was much attenuated among BMDCs stimulated with Y. pestis‐37°. As IL12p40‐homodimer contributes to DC chemotaxis, we also examined the chemotactic ability of Y.pestis‐26° versus Y. pestis‐37° stimulated BMDCs. Stimulation of BMDCs with Y.pestis‐26° significantly increased their chemotaxis towards CCL19 in a dose‐dependent manner, whereas the CCL19‐dependent chemotaxis of Y. pestis‐37° stimulated BMDCs was only minimally increased. Thus, Y.pestis‐26° and Y. pestis‐37° differentially stimulate BMDCs, with the Y. pestis‐37° being associated with diminished IL12p40‐production and chemotaxis.