The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal
Open accessAbstract
BACKGROUND: Characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive Nalp3 inflammasome. Plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. Thus, we hypothesized that hemozoin could activate the Nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. METHODOLOGY/PRINCIPAL FINDINGS: We found that hemozoin acts as a proinflammatory danger signal that activates the Nalp3 inflammasome, causing the release of IL-1beta. Similar to other Nalp3-activating particles, hemozoin activity is blocked by inhibiting phagocytosis, K(+) efflux and NADPH oxidase. In vivo, intraperitoneal injection of hemozoin results in acute peritonitis, which is impaired in Nalp3-, caspase-1- and IL-1R-deficient mice. Likewise, the pathogenesis of cerebral malaria is dampened in Nalp3-deficient mice infected with Plasmodium berghei sporozoites, while parasitemia remains unchanged. SIGNIFICANCE/CONCLUSIONS: The potent pro-inflammatory effect of hemozoin through inflammasome activation may possibly be implicated in plasmodium-associated pathologies such as cerebral malaria.
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Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
Self-citationGout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Self-citationHornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658
Self-citationHaemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator
Hänscheid, T., Egan, T. J., & Grobusch, M. P. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70238-4 · Cited by 128
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Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658
The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation
Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539
Inflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
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Metadata
- Authors
- Dostert, C., Guarda, G., Romero, J. F., Menu, P., Gross, O., Tardivel, A., Suva, M.-L., Stehle, J.-C., Kopf, M., Stamenkovic, I., Corradin, G., & Tschopp, J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-08-04
- Volume
- 4
- Issue
- 8
- Pages
- e6510
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2148795627
- Cited by
- 395
- References
- 5
- FWCI
- 13.68
- Type
- journal article
- Language
- en
- Open access
- gold
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- Dostert, C., Guarda, G., Romero, J. F., Menu, P., Gross, O., Tardivel, A., Suva, M.-L., Stehle, J.-C., Kopf, M., Stamenkovic, I., Corradin, G., & Tschopp, J. (2009). Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal. PLoS ONE. https://doi.org/10.1371/journal.pone.0006510
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