PLoS Pathogens | |
Flagellin-Deficient Legionella Mutants Evade Caspase-1- and Naip5-Mediated Macrophage Immunity | |
Tao Ren1  William F Dietrich1  Russell E Vance1  Dario S Zamboni2  Craig R Roy2  | |
[1] Genetics Department, Harvard Medical School, Boston, Massachusetts, United States of America;Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America | |
关键词: Macrophages; Flagellin; Legionella; Cytotoxicity; Salmonella; Cell death; Transposable elements; Legionella pneumophila; | |
DOI : 10.1371/journal.ppat.0020018 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
Macrophages from C57BL/6J (B6) mice restrict growth of the intracellular bacterial pathogen Legionella pneumophila. Restriction of bacterial growth requires caspase-1 and the leucine-rich repeat-containing protein Naip5 (Birc1e). We identified mutants of L. pneumophila that evade macrophage innate immunity. All mutants were deficient in expression of flagellin, the primary flagellar subunit, and failed to induce caspase-1-mediated macrophage death. Interestingly, a previously isolated flagellar mutant (fliI) that expresses, but does not assemble, flagellin did not replicate in macrophages, and induced macrophage death. Thus, flagellin itself, not flagella or motility, is required to initiate macrophage innate immunity. Immunity to Legionella did not require MyD88, an essential adaptor for toll-like receptor 5 (TLR5) signaling. Moreover, flagellin of Legionella and Salmonella induced cytotoxicity when delivered to the macrophage cytosol using Escherichia coli as a heterologous host. It thus appears that macrophages sense cytosolic flagellin via a TLR5-independent pathway that leads to rapid caspase-1-dependent cell death and provides defense against intracellular bacterial pathogens.
【 授权许可】
CC BY
【 预 览 】
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RO201902015321698ZK.pdf | 309KB | download |