Yersinia pestisType III Secretion System-Dependent Inhibition of Human Polymorphonuclear Leukocyte Function

Abstract

Human polymorphonuclear leukocytes (PMNs, or neutrophils) are the primary innate host defense against invading bacterial pathogens. Neutrophils are rapidly recruited to sites of infection and ingest microorganisms through a process known as phagocytosis. Following phagocytosis by human PMNs, microorganisms are killed by reactive oxygen species (ROS) and microbicidal products contained within granules.Yersinia pestis, the causative agent of plague, is capable of rapid replication and dissemination from sites of infection in the host. AlthoughY. pestissurvives in macrophages, the bacterial fate following interaction with human PMNs is less clear. The ability ofY. pestisto inhibit phagocytosis by human PMNs was assessed by differential fluorescence microscopy and was shown to be dependent on expression of the type III secretion system (TTSS). Previous studies have demonstrated that TTSS expression in enteropathogenicYersiniaspp. also inhibits the respiratory burst in PMNs and macrophages, and we show here that human PMN ROS production is similarly repressed byY. pestis. However, exclusion of uningested TTSS-expressingY. pestiswith gentamicin revealed that intracellular bacteria are eliminated by human PMNs, similar to bacteria lacking the TTSS. In summary, our results suggest that theY. pestisTTSS contributes to extracellular survival following interactions with human PMNs and that the intracellular fate is independent of TTSS inhibition of neutrophil ROS production.