Antibody Opsonization Enhances Early Interactions between Yersinia pestis and Neutrophils in the Skin and Draining Lymph Node in a Mouse Model of Bubonic Plague.

Bubonic plague results when is deposited in the skin via the bite of an infected flea. Bacteria then traffic to the draining lymph node (dLN) where they replicate to large numbers. Without treatment, this infection can result in highly fatal septicemia. Several plague vaccine candidates are currently at various stages of development, but no licensed vaccine is available in the United States. Though polyclonal and monoclonal antibodies (Ab) can provide complete protection against bubonic plague in animal models, the mechanisms responsible for this antibody-mediated immunity (AMI) to remain poorly understood. Here, we examine the effects of Ab opsonization on interactions with phagocytes and Opsonization of with polyclonal antiserum modestly increased phagocytosis/killing by an oxidative burst of murine neutrophils Intravital microscopy (IVM) showed increased association of Ab-opsonized with neutrophils in the dermis in a mouse model of bubonic plague. IVM of popliteal LNs after intradermal (i.d.) injection of bacteria in the footpad revealed increased -neutrophil interactions and increased neutrophil crawling and extravasation in response to Ab-opsonized bacteria. Thus, despite only having a modest effect in assays, opsonizing Ab had a dramatic effect on -neutrophil interactions in the dermis and dLN very early after infection. These data shed new light on the importance of neutrophils in AMI to and may provide a new correlate of protection for evaluation of plague vaccine candidates.