Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria
Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713007596 |
| _version_ | 1819206750750900224 |
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| author | Parisa Kalantari Rosane B. DeOliveira Jennie Chan Yolanda Corbett Vijay Rathinam Andrea Stutz Eicke Latz Ricardo T. Gazzinelli Douglas T. Golenbock Katherine A. Fitzgerald |
| author_facet | Parisa Kalantari Rosane B. DeOliveira Jennie Chan Yolanda Corbett Vijay Rathinam Andrea Stutz Eicke Latz Ricardo T. Gazzinelli Douglas T. Golenbock Katherine A. Fitzgerald |
| author_sort | Parisa Kalantari |
| collection | DOAJ |
| description | Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and DNA dissociate. Hz subsequently induces phagolysosomal destabilization, allowing phagolysosomal contents access to the cytosol, where DNA receptors become activated. Similar observations were made with Plasmodium-infected RBCs. Finally, infected erythrocytes activated both the NLRP3 and AIM2 inflammasomes. These observations suggest that Hz and DNA work together to induce systemic inflammation during malaria. |
| first_indexed | 2024-12-23T05:12:34Z |
| format | Article |
| id | doaj.art-51b2adea720a4100b1781d80f0f6b142 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T05:12:34Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-51b2adea720a4100b1781d80f0f6b1422022-12-21T17:58:56ZengElsevierCell Reports2211-12472014-01-016119621010.1016/j.celrep.2013.12.014Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during MalariaParisa Kalantari0Rosane B. DeOliveira1Jennie Chan2Yolanda Corbett3Vijay Rathinam4Andrea Stutz5Eicke Latz6Ricardo T. Gazzinelli7Douglas T. Golenbock8Katherine A. Fitzgerald9Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, Via Pascal 36, Milano 20133, ItalyDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USAInstitute of Innate Immunity, Biomedical Center, 1G008, University Hospitals, University of Bonn, Sigmund-Freud-Strasse 25, Bonn 53127, GermanyDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USAHemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and DNA dissociate. Hz subsequently induces phagolysosomal destabilization, allowing phagolysosomal contents access to the cytosol, where DNA receptors become activated. Similar observations were made with Plasmodium-infected RBCs. Finally, infected erythrocytes activated both the NLRP3 and AIM2 inflammasomes. These observations suggest that Hz and DNA work together to induce systemic inflammation during malaria.http://www.sciencedirect.com/science/article/pii/S2211124713007596 |
| spellingShingle | Parisa Kalantari Rosane B. DeOliveira Jennie Chan Yolanda Corbett Vijay Rathinam Andrea Stutz Eicke Latz Ricardo T. Gazzinelli Douglas T. Golenbock Katherine A. Fitzgerald Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria Cell Reports |
| title | Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria |
| title_full | Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria |
| title_fullStr | Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria |
| title_full_unstemmed | Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria |
| title_short | Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria |
| title_sort | dual engagement of the nlrp3 and aim2 inflammasomes by plasmodium derived hemozoin and dna during malaria |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713007596 |
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