Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection
| العنوان: | Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection |
|---|---|
| المؤلفون: | Natalie N. Whitfield, Michele S. Swanson, Kazuhiro Tateda, Etsu T. Fuse, Cressida A. Madigan, Brenda G. Byrne, Ari B. Molofsky |
| المصدر: | The Journal of experimental medicine, vol 203, iss 4 The Journal of Experimental Medicine |
| بيانات النشر: | eScholarship, University of California, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Apoptosis, Inbred C57BL, Legionella pneumophila, Medical and Health Sciences, Mice, 0302 clinical medicine, Cytosol, Immunology and Allergy, Macrophage, Innate, 2.1 Biological and endogenous factors, Inbred A, Cells, Cultured, Inbred BALB C, Mice, Knockout, Mice, Inbred BALB C, 0303 health sciences, Cultured, biology, Toll-Like Receptors, Pattern recognition receptor, Listeriolysin O, Adaptor Proteins, Articles, Neuronal Apoptosis-Inhibitory Protein, Infectious Diseases, 030220 oncology & carcinogenesis, Female, Infection, Signal Transduction, Membrane permeability, Mice, Inbred A, Cells, Knockout, Immunology, Article, Microbiology, Vaccine Related, 03 medical and health sciences, Biodefense, Animals, Secretion, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Innate immune system, 030306 microbiology, Macrophages, Prevention, Signal Transducing, Immunity, Cell Biology, biology.organism_classification, Immunity, Innate, Mice, Inbred C57BL, Myeloid Differentiation Factor 88, biology.protein, bacteria, Flagellin |
| الوصف: | To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1β secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52abf2cea52b735b95ed1e6de49b4af4Test https://escholarship.org/uc/item/9d15x5kzTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....52abf2cea52b735b95ed1e6de49b4af4 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |