The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia.

Details

Serval ID
serval:BIB_E8B240F0A085
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia.
Journal
Journal of Immunology
Author(s)
Witzenrath M., Pache F., Lorenz D., Koppe U., Gutbier B., Tabeling C., Reppe K., Meixenberger K., Dorhoi A., Ma J., Holmes A., Trendelenburg G., Heimesaat M.M., Bereswill S., van der Linden M., Tschopp J., Mitchell T.J., Suttorp N., Opitz B.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2011
Volume
187
Number
1
Pages
434-440
Language
english
Abstract
Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and sepsis. Pneumococci can be divided into >90 serotypes that show differences in the pathogenicity and invasiveness. We tested the hypotheses that the innate immune inflammasome pathway is involved in fighting pneumococcal pneumonia and that some invasive pneumococcal types are not recognized by this pathway. We show that human and murine mononuclear cells responded to S. pneumoniae expressing hemolytic pneumolysin by producing IL-1β. This IL-1β production depended on the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Some serotype 1, serotype 8, and serotype 7F bacteria, which have previously been associated with increased invasiveness and with production of toxins with reduced hemolytic activity, or bacterial mutants lacking pneumolysin did not stimulate notable IL-1β production. We further found that NLRP3 was beneficial for mice during pneumonia caused by pneumococci expressing hemolytic pneumolysin and was involved in cytokine production and maintenance of the pulmonary microvascular barrier. Overall, the inflammasome pathway is protective in pneumonia caused by pneumococci expressing hemolytic toxin but is not activated by clinically important pneumococcal sequence types causing invasive disease. The study indicates that a virulence factor polymorphism may substantially affect the recognition of bacteria by the innate immune system.
Keywords
Animals, Bacterial Proteins/biosynthesis, Bacterial Proteins/genetics, Bone Marrow Cells/immunology, Bone Marrow Cells/metabolism, Carrier Proteins/genetics, Carrier Proteins/metabolism, Female, Genetic Predisposition to Disease, Genetic Variation/immunology, Humans, Immunity, Innate/genetics, Inflammasomes/metabolism, Inflammasomes/physiology, Interleukin-18/physiology, Interleukin-1beta/biosynthesis, Macrophages/immunology, Macrophages/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88/deficiency, Myeloid Differentiation Factor 88/genetics, Nod2 Signaling Adaptor Protein/physiology, Pneumonia, Pneumococcal/genetics, Pneumonia, Pneumococcal/immunology, Signal Transduction/genetics, Signal Transduction/immunology, Streptolysins/biosynthesis, Streptolysins/deficiency, Toll-Like Receptor 2/deficiency, Toll-Like Receptor 2/genetics, Toll-Like Receptor 4/deficiency, Toll-Like Receptor 4/genetics, Toll-Like Receptor 9/physiology
Pubmed
Web of science
Open Access
Yes
Create date
02/09/2011 8:58
Last modification date
20/08/2019 16:11
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