Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum
Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variat...
| المؤلفون الرئيسيون: | , , , , , , , , , , , , , , , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
eLife Sciences Publications
2021
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| _version_ | 1826310793399894016 |
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| author | Milne, K Ivens, A Reid, AJ Lotkowska, ME O'Toole, A Sankaranarayanan, G Munoz Sandoval, D Nahrendorf, W Regnault, C Edwards, NJ Silk, SE Payne, RO Minassian, AM Venkatraman, N Sanders, MJ Hill, AV Barrett, M Berriman, M Draper, SJ Rowe, JA Spence, PJ |
| author_facet | Milne, K Ivens, A Reid, AJ Lotkowska, ME O'Toole, A Sankaranarayanan, G Munoz Sandoval, D Nahrendorf, W Regnault, C Edwards, NJ Silk, SE Payne, RO Minassian, AM Venkatraman, N Sanders, MJ Hill, AV Barrett, M Berriman, M Draper, SJ Rowe, JA Spence, PJ |
| author_sort | Milne, K |
| collection | OXFORD |
| description | Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection. |
| first_indexed | 2024-03-07T07:57:14Z |
| format | Journal article |
| id | oxford-uuid:3e374f8d-1f9e-4c0c-b4ad-9fb67e9f276b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:57:14Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:3e374f8d-1f9e-4c0c-b4ad-9fb67e9f276b2023-08-31T15:31:00ZMapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e374f8d-1f9e-4c0c-b4ad-9fb67e9f276bEnglishSymplectic ElementseLife Sciences Publications2021Milne, KIvens, AReid, AJLotkowska, MEO'Toole, ASankaranarayanan, GMunoz Sandoval, DNahrendorf, WRegnault, CEdwards, NJSilk, SEPayne, ROMinassian, AMVenkatraman, NSanders, MJHill, AVBarrett, MBerriman, MDraper, SJRowe, JASpence, PJFalciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection. |
| spellingShingle | Milne, K Ivens, A Reid, AJ Lotkowska, ME O'Toole, A Sankaranarayanan, G Munoz Sandoval, D Nahrendorf, W Regnault, C Edwards, NJ Silk, SE Payne, RO Minassian, AM Venkatraman, N Sanders, MJ Hill, AV Barrett, M Berriman, M Draper, SJ Rowe, JA Spence, PJ Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum |
| title | Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum |
| title_full | Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum |
| title_fullStr | Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum |
| title_full_unstemmed | Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum |
| title_short | Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum |
| title_sort | mapping immune variation and var gene switching in naive hosts infected with plasmodium falciparum |
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