Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression

ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison betw...
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Autor*in:	Clare K. Cimperman [verfasserIn] Mirna Pena [verfasserIn] Sohret M. Gokcek [verfasserIn] Brandon P. Theall [verfasserIn] Meha V. Patel [verfasserIn] Anisha Sharma [verfasserIn] ChenFeng Qi [verfasserIn] Daniel Sturdevant [verfasserIn] Louis H. Miller [verfasserIn] Patrick L. Collins [verfasserIn] Susan K. Pierce [verfasserIn] Munir Akkaya [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria

Übergeordnetes Werk:	In: mBio - American Society for Microbiology, 2010, 14(2023), 2
Übergeordnetes Werk:	volume:14 ; year:2023 ; number:2

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1128/mbio.03391-22

Katalog-ID:	DOAJ089431324

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520			\|a ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches.
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allfields	10.1128/mbio.03391-22 doi (DE-627)DOAJ089431324 (DE-599)DOAJ3261caae55db47f9969e701fac6f0d4d DE-627 ger DE-627 rakwb eng QR1-502 Clare K. Cimperman verfasserin aut Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches. Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria Microbiology Mirna Pena verfasserin aut Sohret M. Gokcek verfasserin aut Brandon P. Theall verfasserin aut Meha V. Patel verfasserin aut Anisha Sharma verfasserin aut ChenFeng Qi verfasserin aut Daniel Sturdevant verfasserin aut Louis H. Miller verfasserin aut Patrick L. Collins verfasserin aut Susan K. Pierce verfasserin aut Munir Akkaya verfasserin aut In mBio American Society for Microbiology, 2010 14(2023), 2 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:14 year:2023 number:2 https://doi.org/10.1128/mbio.03391-22 kostenfrei https://doaj.org/article/3261caae55db47f9969e701fac6f0d4d kostenfrei https://journals.asm.org/doi/10.1128/mbio.03391-22 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2
spelling	10.1128/mbio.03391-22 doi (DE-627)DOAJ089431324 (DE-599)DOAJ3261caae55db47f9969e701fac6f0d4d DE-627 ger DE-627 rakwb eng QR1-502 Clare K. Cimperman verfasserin aut Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches. Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria Microbiology Mirna Pena verfasserin aut Sohret M. Gokcek verfasserin aut Brandon P. Theall verfasserin aut Meha V. Patel verfasserin aut Anisha Sharma verfasserin aut ChenFeng Qi verfasserin aut Daniel Sturdevant verfasserin aut Louis H. Miller verfasserin aut Patrick L. Collins verfasserin aut Susan K. Pierce verfasserin aut Munir Akkaya verfasserin aut In mBio American Society for Microbiology, 2010 14(2023), 2 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:14 year:2023 number:2 https://doi.org/10.1128/mbio.03391-22 kostenfrei https://doaj.org/article/3261caae55db47f9969e701fac6f0d4d kostenfrei https://journals.asm.org/doi/10.1128/mbio.03391-22 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2
allfields_unstemmed	10.1128/mbio.03391-22 doi (DE-627)DOAJ089431324 (DE-599)DOAJ3261caae55db47f9969e701fac6f0d4d DE-627 ger DE-627 rakwb eng QR1-502 Clare K. Cimperman verfasserin aut Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches. Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria Microbiology Mirna Pena verfasserin aut Sohret M. Gokcek verfasserin aut Brandon P. Theall verfasserin aut Meha V. Patel verfasserin aut Anisha Sharma verfasserin aut ChenFeng Qi verfasserin aut Daniel Sturdevant verfasserin aut Louis H. Miller verfasserin aut Patrick L. Collins verfasserin aut Susan K. Pierce verfasserin aut Munir Akkaya verfasserin aut In mBio American Society for Microbiology, 2010 14(2023), 2 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:14 year:2023 number:2 https://doi.org/10.1128/mbio.03391-22 kostenfrei https://doaj.org/article/3261caae55db47f9969e701fac6f0d4d kostenfrei https://journals.asm.org/doi/10.1128/mbio.03391-22 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2
allfieldsGer	10.1128/mbio.03391-22 doi (DE-627)DOAJ089431324 (DE-599)DOAJ3261caae55db47f9969e701fac6f0d4d DE-627 ger DE-627 rakwb eng QR1-502 Clare K. Cimperman verfasserin aut Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches. Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria Microbiology Mirna Pena verfasserin aut Sohret M. Gokcek verfasserin aut Brandon P. Theall verfasserin aut Meha V. Patel verfasserin aut Anisha Sharma verfasserin aut ChenFeng Qi verfasserin aut Daniel Sturdevant verfasserin aut Louis H. Miller verfasserin aut Patrick L. Collins verfasserin aut Susan K. Pierce verfasserin aut Munir Akkaya verfasserin aut In mBio American Society for Microbiology, 2010 14(2023), 2 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:14 year:2023 number:2 https://doi.org/10.1128/mbio.03391-22 kostenfrei https://doaj.org/article/3261caae55db47f9969e701fac6f0d4d kostenfrei https://journals.asm.org/doi/10.1128/mbio.03391-22 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2
allfieldsSound	10.1128/mbio.03391-22 doi (DE-627)DOAJ089431324 (DE-599)DOAJ3261caae55db47f9969e701fac6f0d4d DE-627 ger DE-627 rakwb eng QR1-502 Clare K. Cimperman verfasserin aut Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches. Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria Microbiology Mirna Pena verfasserin aut Sohret M. Gokcek verfasserin aut Brandon P. Theall verfasserin aut Meha V. Patel verfasserin aut Anisha Sharma verfasserin aut ChenFeng Qi verfasserin aut Daniel Sturdevant verfasserin aut Louis H. Miller verfasserin aut Patrick L. Collins verfasserin aut Susan K. Pierce verfasserin aut Munir Akkaya verfasserin aut In mBio American Society for Microbiology, 2010 14(2023), 2 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:14 year:2023 number:2 https://doi.org/10.1128/mbio.03391-22 kostenfrei https://doaj.org/article/3261caae55db47f9969e701fac6f0d4d kostenfrei https://journals.asm.org/doi/10.1128/mbio.03391-22 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2
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topic_facet	Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria Microbiology
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authorswithroles_txt_mv	Clare K. Cimperman @@aut@@ Mirna Pena @@aut@@ Sohret M. Gokcek @@aut@@ Brandon P. Theall @@aut@@ Meha V. Patel @@aut@@ Anisha Sharma @@aut@@ ChenFeng Qi @@aut@@ Daniel Sturdevant @@aut@@ Louis H. Miller @@aut@@ Patrick L. Collins @@aut@@ Susan K. Pierce @@aut@@ Munir Akkaya @@aut@@
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topic_title	QR1-502 Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression Plasmodium cell-mediated immunity cerebral malaria host-parasite relationship malaria
topic	misc QR1-502 misc Plasmodium misc cell-mediated immunity misc cerebral malaria misc host-parasite relationship misc malaria misc Microbiology
topic_unstemmed	misc QR1-502 misc Plasmodium misc cell-mediated immunity misc cerebral malaria misc host-parasite relationship misc malaria misc Microbiology
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title	Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression
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title_full	Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression
author_sort	Clare K. Cimperman
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author_browse	Clare K. Cimperman Mirna Pena Sohret M. Gokcek Brandon P. Theall Meha V. Patel Anisha Sharma ChenFeng Qi Daniel Sturdevant Louis H. Miller Patrick L. Collins Susan K. Pierce Munir Akkaya
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title_sort	cerebral malaria is regulated by host-mediated changes in plasmodium gene expression
callnumber	QR1-502
title_auth	Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression
abstract	ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches.
abstractGer	ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches.
abstract_unstemmed	ABSTRACT Cerebral malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. However, our understanding of the host and parasite factors that cause CM is limited. Using a mouse model of CM, experimental CM (ECM), we performed a three-way comparison between ECM-susceptible C57BL/6 mice infected with ECM-causing Plasmodium ANKA parasites [ANKA(C57BL/6)], ECM-resistant BALB/c mice infected with Plasmodium ANKA [ANKA(BALB/c)], and C57BL/6 mice infected with Plasmodium NK65 that does not cause ECM [NK65(C57BL/6)]. All ANKA(C57BL/6) mice developed CM. In contrast, in ANKA(BALB/c) and NK65(C57BL/6), infections do not result in CM and proceed similarly in terms of parasite growth, disease course, and host immune response. However, parasite gene expression in ANKA(BALB/c) was remarkably different than that in ANKA(C57BL/6) but similar to the gene expression in NK65(C57BL/6). Thus, Plasmodium ANKA has an ECM-specific gene expression profile that is activated only in susceptible hosts, providing evidence that the host has a critical influence on the outcome of infection. IMPORTANCE Hundreds of thousands of lives are lost each year due to the brain damage caused by malaria disease. The overwhelming majority of these deaths occur in young children living in sub-Saharan Africa. Thus far, there are no vaccines against this deadly disease, and we still do not know why fatal brain damage occurs in some children while others have milder, self-limiting disease progression. Our research provides an important clue to this problem. Here, we showed that the genetic background of the host has an important role in determining the course and the outcome of the disease. Our research also identified parasite molecules that can potentially be targeted in vaccination and therapy approaches.
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title_short	Cerebral Malaria Is Regulated by Host-Mediated Changes in Plasmodium Gene Expression
url	https://doi.org/10.1128/mbio.03391-22 https://doaj.org/article/3261caae55db47f9969e701fac6f0d4d https://journals.asm.org/doi/10.1128/mbio.03391-22 https://doaj.org/toc/2150-7511
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author2	Mirna Pena Sohret M. Gokcek Brandon P. Theall Meha V. Patel Anisha Sharma ChenFeng Qi Daniel Sturdevant Louis H. Miller Patrick L. Collins Susan K. Pierce Munir Akkaya
author2Str	Mirna Pena Sohret M. Gokcek Brandon P. Theall Meha V. Patel Anisha Sharma ChenFeng Qi Daniel Sturdevant Louis H. Miller Patrick L. Collins Susan K. Pierce Munir Akkaya
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up_date	2024-07-03T23:03:13.294Z
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