Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells
The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockou...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Urvashi N. Ramphul [verfasserIn] |
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| Format: |
Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015 |
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| Rechteinformationen: |
Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences |
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| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 112(2015), 5, Seite 1273-1280 |
|---|---|
| Übergeordnetes Werk: |
volume:112 ; year:2015 ; number:5 ; pages:1273-1280 |
| Links: |
Volltext |
|---|
| DOI / URN: |
10.1073/pnas.1423586112 |
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| Katalog-ID: |
OLC1961712164 |
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| 245 | 1 | 0 | |a Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells |
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| 520 | |a The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. | ||
| 540 | |a Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences | ||
| 650 | 4 | |a Apoptosis - physiology | |
| 650 | 4 | |a Plasmodium falciparum - physiology | |
| 650 | 4 | |a Protozoan Proteins - genetics | |
| 650 | 4 | |a Protozoan Proteins - physiology | |
| 650 | 4 | |a Membrane Glycoproteins - physiology | |
| 650 | 4 | |a Plasmodium falciparum - genetics | |
| 650 | 4 | |a Anopheles gambiae - immunology | |
| 650 | 4 | |a MAP Kinase Kinase 4 - metabolism | |
| 650 | 4 | |a Anopheles gambiae - parasitology | |
| 650 | 4 | |a Membrane Glycoproteins - genetics | |
| 650 | 4 | |a Observations | |
| 650 | 4 | |a Mosquitoes | |
| 650 | 4 | |a Plasmodium falciparum | |
| 650 | 4 | |a Immune response | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Health aspects | |
| 650 | 4 | |a Gene expression | |
| 650 | 4 | |a Parasites | |
| 650 | 4 | |a Malaria | |
| 650 | 4 | |a Cells | |
| 650 | 4 | |a malaria transmission | |
| 650 | 4 | |a JNK apoptosis | |
| 650 | 4 | |a Plasmodium | |
| 650 | 4 | |a Biological Sciences | |
| 650 | 4 | |a mosquito immunity | |
| 650 | 4 | |a immune evasion | |
| 700 | 0 | |a Lindsey S. Garver |4 oth | |
| 700 | 0 | |a Alvaro Molina-Cruz |4 oth | |
| 700 | 0 | |a Gaspar E. Canepa |4 oth | |
| 700 | 0 | |a Carolina Barillas-Mury |4 oth | |
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10.1073/pnas.1423586112 doi PQ20160617 (DE-627)OLC1961712164 (DE-599)GBVOLC1961712164 (PRQ)g2649-544dc48ad24999b642d960fa21335f426da21214a6ef4191fe869c5bbc7690033 (KEY)0583363920150000112000501273plasmodiumfalciparumevadesmosquitoimmunitybydisrup DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Urvashi N. Ramphul verfasserin aut Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Apoptosis - physiology Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - physiology Membrane Glycoproteins - physiology Plasmodium falciparum - genetics Anopheles gambiae - immunology MAP Kinase Kinase 4 - metabolism Anopheles gambiae - parasitology Membrane Glycoproteins - genetics Observations Mosquitoes Plasmodium falciparum Immune response Apoptosis Health aspects Gene expression Parasites Malaria Cells malaria transmission JNK apoptosis Plasmodium Biological Sciences mosquito immunity immune evasion Lindsey S. Garver oth Alvaro Molina-Cruz oth Gaspar E. Canepa oth Carolina Barillas-Mury oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 5, Seite 1273-1280 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:5 pages:1273-1280 http://dx.doi.org/10.1073/pnas.1423586112 Volltext http://www.pnas.org/content/112/5/1273.abstract http://www.ncbi.nlm.nih.gov/pubmed/25552553 http://search.proquest.com/docview/1652779804 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4321252&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 5 1273-1280 |
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10.1073/pnas.1423586112 doi PQ20160617 (DE-627)OLC1961712164 (DE-599)GBVOLC1961712164 (PRQ)g2649-544dc48ad24999b642d960fa21335f426da21214a6ef4191fe869c5bbc7690033 (KEY)0583363920150000112000501273plasmodiumfalciparumevadesmosquitoimmunitybydisrup DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Urvashi N. Ramphul verfasserin aut Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Apoptosis - physiology Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - physiology Membrane Glycoproteins - physiology Plasmodium falciparum - genetics Anopheles gambiae - immunology MAP Kinase Kinase 4 - metabolism Anopheles gambiae - parasitology Membrane Glycoproteins - genetics Observations Mosquitoes Plasmodium falciparum Immune response Apoptosis Health aspects Gene expression Parasites Malaria Cells malaria transmission JNK apoptosis Plasmodium Biological Sciences mosquito immunity immune evasion Lindsey S. Garver oth Alvaro Molina-Cruz oth Gaspar E. Canepa oth Carolina Barillas-Mury oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 5, Seite 1273-1280 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:5 pages:1273-1280 http://dx.doi.org/10.1073/pnas.1423586112 Volltext http://www.pnas.org/content/112/5/1273.abstract http://www.ncbi.nlm.nih.gov/pubmed/25552553 http://search.proquest.com/docview/1652779804 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4321252&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 5 1273-1280 |
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10.1073/pnas.1423586112 doi PQ20160617 (DE-627)OLC1961712164 (DE-599)GBVOLC1961712164 (PRQ)g2649-544dc48ad24999b642d960fa21335f426da21214a6ef4191fe869c5bbc7690033 (KEY)0583363920150000112000501273plasmodiumfalciparumevadesmosquitoimmunitybydisrup DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Urvashi N. Ramphul verfasserin aut Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Apoptosis - physiology Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - physiology Membrane Glycoproteins - physiology Plasmodium falciparum - genetics Anopheles gambiae - immunology MAP Kinase Kinase 4 - metabolism Anopheles gambiae - parasitology Membrane Glycoproteins - genetics Observations Mosquitoes Plasmodium falciparum Immune response Apoptosis Health aspects Gene expression Parasites Malaria Cells malaria transmission JNK apoptosis Plasmodium Biological Sciences mosquito immunity immune evasion Lindsey S. Garver oth Alvaro Molina-Cruz oth Gaspar E. Canepa oth Carolina Barillas-Mury oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 5, Seite 1273-1280 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:5 pages:1273-1280 http://dx.doi.org/10.1073/pnas.1423586112 Volltext http://www.pnas.org/content/112/5/1273.abstract http://www.ncbi.nlm.nih.gov/pubmed/25552553 http://search.proquest.com/docview/1652779804 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4321252&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 5 1273-1280 |
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10.1073/pnas.1423586112 doi PQ20160617 (DE-627)OLC1961712164 (DE-599)GBVOLC1961712164 (PRQ)g2649-544dc48ad24999b642d960fa21335f426da21214a6ef4191fe869c5bbc7690033 (KEY)0583363920150000112000501273plasmodiumfalciparumevadesmosquitoimmunitybydisrup DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Urvashi N. Ramphul verfasserin aut Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Apoptosis - physiology Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - physiology Membrane Glycoproteins - physiology Plasmodium falciparum - genetics Anopheles gambiae - immunology MAP Kinase Kinase 4 - metabolism Anopheles gambiae - parasitology Membrane Glycoproteins - genetics Observations Mosquitoes Plasmodium falciparum Immune response Apoptosis Health aspects Gene expression Parasites Malaria Cells malaria transmission JNK apoptosis Plasmodium Biological Sciences mosquito immunity immune evasion Lindsey S. Garver oth Alvaro Molina-Cruz oth Gaspar E. Canepa oth Carolina Barillas-Mury oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 5, Seite 1273-1280 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:5 pages:1273-1280 http://dx.doi.org/10.1073/pnas.1423586112 Volltext http://www.pnas.org/content/112/5/1273.abstract http://www.ncbi.nlm.nih.gov/pubmed/25552553 http://search.proquest.com/docview/1652779804 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4321252&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 5 1273-1280 |
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10.1073/pnas.1423586112 doi PQ20160617 (DE-627)OLC1961712164 (DE-599)GBVOLC1961712164 (PRQ)g2649-544dc48ad24999b642d960fa21335f426da21214a6ef4191fe869c5bbc7690033 (KEY)0583363920150000112000501273plasmodiumfalciparumevadesmosquitoimmunitybydisrup DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Urvashi N. Ramphul verfasserin aut Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Apoptosis - physiology Plasmodium falciparum - physiology Protozoan Proteins - genetics Protozoan Proteins - physiology Membrane Glycoproteins - physiology Plasmodium falciparum - genetics Anopheles gambiae - immunology MAP Kinase Kinase 4 - metabolism Anopheles gambiae - parasitology Membrane Glycoproteins - genetics Observations Mosquitoes Plasmodium falciparum Immune response Apoptosis Health aspects Gene expression Parasites Malaria Cells malaria transmission JNK apoptosis Plasmodium Biological Sciences mosquito immunity immune evasion Lindsey S. Garver oth Alvaro Molina-Cruz oth Gaspar E. Canepa oth Carolina Barillas-Mury oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 5, Seite 1273-1280 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:5 pages:1273-1280 http://dx.doi.org/10.1073/pnas.1423586112 Volltext http://www.pnas.org/content/112/5/1273.abstract http://www.ncbi.nlm.nih.gov/pubmed/25552553 http://search.proquest.com/docview/1652779804 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4321252&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 5 1273-1280 |
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Urvashi N. Ramphul ddc 500 ddc 570 fid LING fid BIODIV misc Apoptosis - physiology misc Plasmodium falciparum - physiology misc Protozoan Proteins - genetics misc Protozoan Proteins - physiology misc Membrane Glycoproteins - physiology misc Plasmodium falciparum - genetics misc Anopheles gambiae - immunology misc MAP Kinase Kinase 4 - metabolism misc Anopheles gambiae - parasitology misc Membrane Glycoproteins - genetics misc Observations misc Mosquitoes misc Plasmodium falciparum misc Immune response misc Apoptosis misc Health aspects misc Gene expression misc Parasites misc Malaria misc Cells misc malaria transmission misc JNK apoptosis misc Plasmodium misc Biological Sciences misc mosquito immunity misc immune evasion Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells |
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Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells |
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The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. |
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The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. |
| abstract_unstemmed |
The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system. |
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Ramphul</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system.</subfield></datafield><datafield tag="540" ind1=" " ind2=" "><subfield code="a">Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Apoptosis - physiology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Plasmodium falciparum - physiology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Protozoan Proteins - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Protozoan Proteins - physiology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Membrane Glycoproteins - physiology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Plasmodium falciparum - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Anopheles gambiae - immunology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">MAP Kinase Kinase 4 - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Anopheles gambiae - parasitology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Membrane Glycoproteins - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Observations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mosquitoes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Plasmodium falciparum</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immune response</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Apoptosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Health aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene expression</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Parasites</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Malaria</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cells</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">malaria transmission</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">JNK apoptosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Plasmodium</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Biological Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mosquito immunity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">immune evasion</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lindsey S. Garver</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alvaro Molina-Cruz</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gaspar E. Canepa</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carolina Barillas-Mury</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">112(2015), 5, Seite 1273-1280</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:112</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:5</subfield><subfield code="g">pages:1273-1280</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1423586112</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pnas.org/content/112/5/1273.abstract</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.ncbi.nlm.nih.gov/pubmed/25552553</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://search.proquest.com/docview/1652779804</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4321252&tool=pmcentrez&rendertype=abstract</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">112</subfield><subfield code="j">2015</subfield><subfield code="e">5</subfield><subfield code="h">1273-1280</subfield></datafield></record></collection>
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