Shigella flexneri is trapped in polymorphonuclear leukocyte vacuoles and efficiently killed

Abstract

We examined the bactericidal activity of polymorphonuclear leukocytes (PMN) against an invasive wild-type strain of Shigella flexneri (M90T) and a plasmid-cured noninvasive derivative (BS176). Both Shigella strains, as well as a rough strain of Escherichia coli, were killed with similar efficiencies by intact inflammatory PMN in room air and under N 2 (i.e., killing was O 2 independent). Bacterial killing by PMN extracts was substantially inhibited by antibodies to the bactericidal/permeability-increasing protein (BPI). Whereas wild-type Shigella escapes from the phagosome to the cytoplasm in epithelial cells and macrophages, wild-type Shigella was trapped in the phagolysosome of PMN as visualized by electron microscopy. The efficient killing of Shigella by PMN suggests that these inflammatory cells may not only contribute initially to the severe tissue damage characteristic of shigellosis but also ultimately participate in clearance and resolution of infection.

Pivotal Advance: Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape

“…In particular, it is noteworthy that Listeria monocytogenes and Shigella flexneri escape the phagosome in macrophages and/or epithelial cells, but neither of these organisms evades killing by neutrophils. Shigella virulence factors required for phagosome escape are degraded by PMN elastase [20,21], and Listeria is rapidly killed by intraphagosomal ROS [15]. Conversely, Anaplasma phagocytophilum is an obligate intracellular pathogen of neutrophils.…”

Rupture, invasion and inflammatory destruction of the intestinal barrier by Shigella, making sense of prokaryote–eukaryote cross-talks

“…In the presence of lipopolysaccharide (LPS)-activated macrophages, invasive Shigella survive and grow, they quickly induce apoptosis and cause massive secretion of interleukin (IL)-1L [6] and IL-18, factors that are likely to play a central role in initiating in£ammation. In the presence of polymorphonuclear leukocytes (PMN) invasive Shigella cause increased adherence and release of granular content, thereby adding to the severity of in£ammation [7], although Shigella is unable to survive in those activated PMNs [8].…”

Multifaceted effects of Francisella tularensis on human neutrophil function and lifespan

“…Approximately 4 h after uptake the phagosome membrane is breached, bacteria are released into the cytosol and begin to replicate in this locale (100,142). Thus, F. tularensis is one of few pathogens that can grow in neutrophils as well as mononuclear phagocytes (8,36,100,143,144), and a light microscopy image of bacteria replicating in PMN cytosol is shown in Fig. 2.…”