Journal article
AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes
Proceedings of the National Academy of Sciences - PNAS, Vol.120(2), e2210181120
01/10/2023
DOI: 10.1073/pnas.2210181120
PMCID: PMC9926219
PMID: 36595704
Abstract
Malaria, caused by Plasmodium parasites is a severe disease affecting millions of people around the world. Plasmodium undergoes obligatory development and replication in the hepatocytes, before initiating the life-threatening blood-stage of malaria. Although the natural immune responses impeding Plasmodium infection and development in the liver are key to controlling clinical malaria and transmission, those remain relatively unknown. Here we demonstrate that the DNA of Plasmodium parasites is sensed by cytosolic AIM2 (absent in melanoma 2) receptors in the infected hepatocytes, resulting in Caspase-1 activation. Remarkably, Caspase-1 was observed to undergo unconventional proteolytic processing in hepatocytes, resulting in the activation of the membrane pore-forming protein, Gasdermin D, but not inflammasome-associated proinflammatory cytokines. Nevertheless, this resulted in the elimination of Plasmodium -infected hepatocytes and the control of malaria infection in the liver. Our study uncovers a pathway of natural immunity critical for the control of malaria in the liver.
Details
- Title: Subtitle
- AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes
- Creators
- Camila Marques-da-Silva - Department of Cellular Biology, University of Georgia, Athens, GA 30605, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605Barun Poudel - University of IowaRodrigo P. Baptista - Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605, Institute of Bioinformatics, University of Georgia, Athens, GA 30605Kristen Peissig - Department of Cellular Biology, University of Georgia, Athens, GA 30605, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605Lisa S. Hancox - Department of Pathology, University of Iowa, Iowa City, IA 52242Justine C. Shiau - Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605, Department of Infectious Diseases, University of Georgia, Athens, GA 30605Lecia L. Pewe - University of IowaMelanie J. Shears - Johns Hopkins UniversityThirumala-Devi Kanneganti - St. Jude Children's Research HospitalPhotini Sinnis - Johns Hopkins UniversityDennis E. Kyle - Department of Cellular Biology, University of Georgia, Athens, GA 30605, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605, Department of Infectious Diseases, University of Georgia, Athens, GA 30605Prajwal Gurung - University of IowaJohn T. Harty - Department of Pathology, University of Iowa, Iowa City, IA 52242, Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242Samarchith P. Kurup - University of Georgia
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.120(2), e2210181120
- DOI
- 10.1073/pnas.2210181120
- PMID
- 36595704
- PMCID
- PMC9926219
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Grant note
- DOI: 10.13039/100012483, name: UGA | University of Georgia Research Foundation, award: Kurup Startup; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: AI168307; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: AI85515 AI95178 AI100527; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: AI132359; DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: K22AI127836
- Language
- English
- Date published
- 01/10/2023
- Academic Unit
- Infectious Diseases; Stead Family Department of Pediatrics; Pathology; Internal Medicine
- Record Identifier
- 9984354958902771
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