G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection
Epidemiological studies provide compelling evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency individuals are relatively protected against Plasmodium parasite infection. However, the animal model studies on this subject are lacking. Plus, the underlying mechanism in vivo is poorly kno...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.719189/full |
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| author | Haoan Yi Weiyang Jiang Fang Yang Fan Li Yirong Li Wenjing Zhu Qing Li Syed Hassam Fakhar Yaming Cao Lan Luo Wen Zhang Yongshu He |
| author_facet | Haoan Yi Weiyang Jiang Fang Yang Fan Li Yirong Li Wenjing Zhu Qing Li Syed Hassam Fakhar Yaming Cao Lan Luo Wen Zhang Yongshu He |
| author_sort | Haoan Yi |
| collection | DOAJ |
| description | Epidemiological studies provide compelling evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency individuals are relatively protected against Plasmodium parasite infection. However, the animal model studies on this subject are lacking. Plus, the underlying mechanism in vivo is poorly known. In this study, we used a G6pd-deficient mice infected with the rodent parasite Plasmodium berghei (P.berghei) to set up a malaria model in mice. We analyzed the pathological progression of experimental cerebral malaria (ECM) and acute liver injury in mice with different G6pd activity infected with P.berghei. We performed dual RNA-seq for host-parasite transcriptomics and validated the changes of proinflammatory response in the murine model. G6pd-deficient mice exhibited a survival advantage, less severe ECM and mild liver injury compared to the wild type mice. Analysis based on dual RNA-seq suggests that G6pd-deficient mice are protected from ECM and acute liver injury were related to proinflammatory responses. Th1 differentiation and dendritic cell maturation in the liver and spleen were inhibited in G6pd-deficient mice. The levels of proinflammatory cytokines were reduced, chemokines and vascular adhesion molecules in the brain were significantly down-regulated, these led to decreased cerebral microvascular obstruction in G6pd-deficient mice. We generated the result that G6pd-deficiency mediated protection against ECM and acute liver injury were driven by the regulatory proinflammatory responses. Furthermore, bioinformatics analyses showed that P.berghei might occur ribosome loss in G6pd-deficient mice. Our findings provide a novel perspective of the underlying mechanism of G6PD deficiency mediated protection against malaria in vivo. |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T08:56:25Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ea6cd2c29a924a2b8a508b2f4fc25c7b2022-12-21T21:55:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.719189719189G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei InfectionHaoan Yi0Weiyang Jiang1Fang Yang2Fan Li3Yirong Li4Wenjing Zhu5Qing Li6Syed Hassam Fakhar7Yaming Cao8Lan Luo9Wen Zhang10Yongshu He11Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaDepartment of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaDepartment of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaDepartment of Pathology and Pathophysiology, Kunming Medical University, Kunming, ChinaSchool of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, ChinaDepartment of Human Anatomy/Histology and Embryology, School of Basic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaSchool of Public Health, Kunming Medical University, Kunming, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaDepartment of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaDepartment of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, ChinaEpidemiological studies provide compelling evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency individuals are relatively protected against Plasmodium parasite infection. However, the animal model studies on this subject are lacking. Plus, the underlying mechanism in vivo is poorly known. In this study, we used a G6pd-deficient mice infected with the rodent parasite Plasmodium berghei (P.berghei) to set up a malaria model in mice. We analyzed the pathological progression of experimental cerebral malaria (ECM) and acute liver injury in mice with different G6pd activity infected with P.berghei. We performed dual RNA-seq for host-parasite transcriptomics and validated the changes of proinflammatory response in the murine model. G6pd-deficient mice exhibited a survival advantage, less severe ECM and mild liver injury compared to the wild type mice. Analysis based on dual RNA-seq suggests that G6pd-deficient mice are protected from ECM and acute liver injury were related to proinflammatory responses. Th1 differentiation and dendritic cell maturation in the liver and spleen were inhibited in G6pd-deficient mice. The levels of proinflammatory cytokines were reduced, chemokines and vascular adhesion molecules in the brain were significantly down-regulated, these led to decreased cerebral microvascular obstruction in G6pd-deficient mice. We generated the result that G6pd-deficiency mediated protection against ECM and acute liver injury were driven by the regulatory proinflammatory responses. Furthermore, bioinformatics analyses showed that P.berghei might occur ribosome loss in G6pd-deficient mice. Our findings provide a novel perspective of the underlying mechanism of G6PD deficiency mediated protection against malaria in vivo.https://www.frontiersin.org/articles/10.3389/fimmu.2021.719189/fullG6PD deficiencyPlasmodium bergheiproinflammatory responseexperimental cerebral malariaacute liver injury |
| spellingShingle | Haoan Yi Weiyang Jiang Fang Yang Fan Li Yirong Li Wenjing Zhu Qing Li Syed Hassam Fakhar Yaming Cao Lan Luo Wen Zhang Yongshu He G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection Frontiers in Immunology G6PD deficiency Plasmodium berghei proinflammatory response experimental cerebral malaria acute liver injury |
| title | G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection |
| title_full | G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection |
| title_fullStr | G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection |
| title_full_unstemmed | G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection |
| title_short | G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection |
| title_sort | g6pd deficient mice are protected from experimental cerebral malaria and liver injury by suppressing proinflammatory response in the early stage of plasmodium berghei infection |
| topic | G6PD deficiency Plasmodium berghei proinflammatory response experimental cerebral malaria acute liver injury |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.719189/full |
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