Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes.
In: Blood, Jg. 118 (2011-08-18), Heft 7, S. 1923-33
Online
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Zugriff:
The Plasmodium falciparum adhesin PfRh4 binds to complement receptor type-1 (CR1) on human erythrocytes and mediates a glycophorin-independent invasion pathway. CR1 is a complement regulator and immune-adherence receptor on erythrocytes required for shuttling of C3b/C4b-opsonized particles to liver and spleen for phagocytosis. Using recombinant CR1 constructs, we mapped the recognition site for PfRh4 to complement control protein modules 1 to 3 (CCP1-3) at the membrane-distal amino terminus of CR1. This region of CR1 binds to C4b and C3b and accelerates decay of both classic pathway and alternative pathway C3 and C5 convertases. CCP1-3 competed for PfRh4 binding to erythroid CR1 and inhibited the PfRh4-CR1 invasion pathways across a wide range of P falciparum strains. PfRh4 did not bind significantly to other CR1 constructs, including CCP15-17, which is 85% identical to CCP1-3. PfRh4 binding to CR1 did not affect its C3b/C4b binding capability, and we show evidence for a ternary complex between CCP1-3, C4b, and PfRh4. PfRh4 binding specifically inhibited CR1's convertase decay-accelerating activity, whereas there was no effect on factor H-mediated decay-accelerating activity. These results increase our understanding of the functional implications of CR1 engagement with PfRh4 and highlight the interplay between complement regulation and infection.
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Plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes.
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Autor/in / Beteiligte Person: | Tham, WH ; Schmidt, CQ ; Hauhart, RE ; Guariento, M ; Tetteh-Quarcoo, PB ; Lopaticki, S ; Atkinson, JP ; Barlow, PN ; Cowman, AF |
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Zeitschrift: | Blood, Jg. 118 (2011-08-18), Heft 7, S. 1923-33 |
Veröffentlichung: | 2021- : [New York] : Elsevier ; <i>Original Publication</i>: New York, Grune & Stratton [etc.], 2011 |
Medientyp: | academicJournal |
ISSN: | 1528-0020 (electronic) |
DOI: | 10.1182/blood-2011-03-341305 |
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