Affiliation:
1. Department of Internal Medicine1 and
2. Division of Cell Biology and Immunology, National Center for Biotechnology, Braunschweig,2 Germany
3. Institute of Medical Microbiology,3 Justus-Liebig-University, Giessen, and
Abstract
ABSTRACT
Polymorphonuclear leukocytes (PMN) are essential for resolution of infections with
Listeria monocytogenes
. The present study investigated the role of the listerial exotoxins listeriolysin (LLO) and phosphatidylinositol-specific phospholipase C (PlcA) in human neutrophil activation. Different
Listeria
strains, mutated in individual virulence genes, as well as purified LLO were used. Coincubation of human neutrophils with wild-type
L. monocytogenes
provoked PMN activation, occurring independently of phagocytosis events, with concomitant elastase secretion, leukotriene generation, platelet-activating factor (PAF) synthesis, respiratory burst, and enhanced phosphoinositide hydrolysis. Degranulation and leukotriene formation were noted to be solely dependent on LLO expression, as these features were absent when the LLO-defective mutant EGD− and the avirulent strain
L. innocua
were used. These effects were fully reproduced by a recombinant
L. innocua
strain expressing LLO (INN+) and by the purified LLO molecule. LLO secretion was also required for PAF synthesis. However, wild-type
L. monocytogenes
was more potent in eliciting PAF formation than mutants expressing LLO, suggesting the involvement of additional virulence factors. This was even more obvious for phosphoinositide hydrolysis and respiratory burst: these events were provoked not only by INN+ but also by the LLO-defective mutant EGD− and by a recombinant
L. innocua
strain producing listerial PlcA. We conclude that human neutrophils react to extracellularly provided listerial exotoxins by rapid cell activation. Listeriolysin is centrally involved in triggering degranulation and lipid mediator generation, and further virulence factors such as PlcA apparently contribute to trigger neutrophil phosphoinositide hydrolysis and respiratory burst. In this way, listerial exotoxins may influence the host defense against infections with
L. monocytogenes
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
53 articles.
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