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Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis
Open accessAbstract
Francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. This bacterial pathogen causes a plague-like disease in humans after exposure to as few as 10 cells. Many of the mechanisms by which the innate immune system fights Francisella are unknown. Here we show that wild-type Francisella, which reach the cytosol, but not Francisella mutants that remain localized to the vacuole, induced a host defense response in macrophages, which is dependent on caspase-1 and the death-fold containing adaptor protein ASC. Caspase-1 and ASC signaling resulted in host cell death and the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18. F. tularensis–infected caspase-1– and ASC-deficient mice showed markedly increased bacterial burdens and mortality as compared with wild-type mice, demonstrating a key role for caspase-1 and ASC in innate defense against infection by this pathogen.
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Cited by
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Pyroptosis: Mechanisms and Diseases
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., & Chen, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00507-5 · Cited by 2,353
Dominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., et al. (2019) · Science Advances · doi:10.1126/sciadv.aau3333 · Cited by 1,966
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Metadata
- Authors
- Mariathasan, S., Weiss, D. S., Dixit, V. M., & Monack, D. M.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-10-17
- Volume
- 202
- Issue
- 8
- Pages
- 1043-1049
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2133515094
- Cited by
- 402
- References
- 0
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- green
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- Mariathasan, S., Weiss, D. S., Dixit, V. M., & Monack, D. M. (2005). Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20050977
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