AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes.

Autor:	Marques-da-Silva C; Department of Cellular Biology, University of Georgia, Athens, GA 30605.; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605., Poudel B; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242., Baptista RP; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605.; Institute of Bioinformatics, University of Georgia, Athens, GA 30605., Peissig K; Department of Cellular Biology, University of Georgia, Athens, GA 30605.; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605., Hancox LS; Department of Pathology, University of Iowa, Iowa City, IA 52242., Shiau JC; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605.; Department of Infectious Diseases, University of Georgia, Athens, GA 30605., Pewe LL; Department of Pathology, University of Iowa, Iowa City, IA 52242., Shears MJ; Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, MD 21205.; Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD 21205., Kanneganti TD; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105., Sinnis P; Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, MD 21205.; Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD 21205., Kyle DE; 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 30605., Gurung P; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242.; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242., Harty JT; Department of Pathology, University of Iowa, Iowa City, IA 52242.; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242., Kurup SP; Department of Cellular Biology, University of Georgia, Athens, GA 30605.; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Jan 10; Vol. 120 (2), pp. e2210181120. Date of Electronic Publication: 2023 Jan 03.
DOI:	10.1073/pnas.2210181120
Abstrakt:	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.
Databáze:	MEDLINE
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