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Cited by 183

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection

Open access
Ataide, Marco A., Andrade, Warrison A., Zamboni, Dario S., Wang, Donghai, Souza, Maria do Carmo, Franklin, Bernardo S., Elian, Samir, Martins, Flaviano S., Pereira, Dhelio, Reed, George, Fitzgerald, Katherine A., Golenbock, Douglas T., Gazzinelli, Ricardo T.·2014·PLoS Pathogens

Abstract

Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14(+)CD16(-)Caspase-1(+) and CD14(dim)CD16(+)Caspase-1(+) monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria.

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Metadata

Authors
Ataide, M. A., Andrade, W. A., Zamboni, D. S., Wang, D., Souza, M. D. C., Franklin, B. S., Elian, S., Martins, F. S., Pereira, D., Reed, G., Fitzgerald, K. A., Golenbock, D. T., & Gazzinelli, R. T.
Venue
PLoS Pathogens
Published
2014-01-16
Volume
10
Issue
1
Pages
e1003885
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
OpenAlex
W1964465730
Cited by
183
References
15
FWCI
7.30
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection. https://app.cochat.ai/papers/10.1371/journal.ppat.1003885
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Ataide, M. A., Andrade, W. A., Zamboni, D. S., Wang, D., Souza, M. D. C., Franklin, B. S., Elian, S., Martins, F. S., Pereira, D., Reed, G., Fitzgerald, K. A., Golenbock, D. T., & Gazzinelli, R. T. (2014). Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1003885

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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