The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection
Open accessAbstract
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.
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Cites
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Pyroptosis: host cell death and inflammation
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Caspase Functions in Cell Death and Disease
McIlwain, D. R., Berger, T., & Mak, T. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008656 · Cited by 2,594
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,206
Metadata
- Authors
- Molofsky, A. B., Byrne, B. G., Whitfield, N. N., Madigan, C. A., Fuse, E. T., Tateda, K., & Swanson, M. S.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-04-10
- Volume
- 203
- Issue
- 4
- Pages
- 1093-1104
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2161320421
- Cited by
- 489
- References
- 68
- FWCI
- 19.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Molofsky, A. B., Byrne, B. G., Whitfield, N. N., Madigan, C. A., Fuse, E. T., Tateda, K., & Swanson, M. S. (2006). Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20051659
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