Discordance in the Effects ofYersinia pestison the Dendritic Cell Functions Manifested by Induction of Maturation and Paralysis of Migration

Abstract

The encounter between invading microorganisms and dendritic cells (DC) triggers a series of events which include uptake and degradation of the microorganism, induction of a maturation process, and enhancement of DC migration to the draining lymph nodes. Various pathogens have developed strategies to counteract these events as a measure to evade the host defense. In the present study we found that interaction of theYersinia pestisEV76 strain with DC has no effect on cell viability and is characterized by compliance with effective maturation, which is manifested by surface display of major histocompatibility complex class II, of costimulatory markers, and of the chemokine receptor CCR7. This is in contrast to maturation inhibition and cell death induction exerted by the related speciesYersinia enterocoliticaWA O:8.Y. pestisinteractions with DC were found, however, to impair functions related to cytoskeleton rearrangement. DC pulsed withY. pestisfailed to adhere to solid surfaces and to migrate toward the chemokine CCL19 in an in vitro transmembrane assay. Both effects were dependent on the presence of the pCD1 virulence plasmid and on a bacterial growth shift to 37°C prior to infection. Moreover, while instillation of a pCD1-curedY. pestisstrain into mouse airways triggered effective transport of alveolar DC to the mediastinal lymph node, instillation ofY. pestisharboring the plasmid failed to do so. Taken together, these results suggest that virulence plasmid-dependent impairment of DC migration is the major mechanism utilized byY. pestisto subvert DC function.