期刊
CELLULAR MICROBIOLOGY
卷 17, 期 6, 页码 819-831出版社
WILEY
DOI: 10.1111/cmi.12403
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资金
- Danish Council for Independent Research [DFF-FSS 11-115707, 11-120879]
- European Community [242095 - EVIMalaR]
- Lundbeck Foundation [R839-A7627]
- Novo Nordisk Foundation
- University of Copenhagen
- EVIMalaR
- Wellcome Trust [084226]
- DFF-FSS
- Lundbeck Foundation [R83-2011-7627] Funding Source: researchfish
Acquired protection from Plasmodium falciparum malaria takes years to develop, probably reflecting the ability of the parasites to evade immunity. A recent example of this is the binding of the F-c region of IgM to VAR2CSA-type PfEMP1. This interferes with specific IgG recognition and phagocytosis of opsonized infected erythrocytes (IEs) without compromising the placental IE adhesion mediated by this PfEMP1 type. IgM also binds via F-c to several other PfEMP1 proteins, where it has been proposed to facilitate rosetting (binding of uninfected erythrocytes to a central IE). To further dissect the functional role of F-c-mediated IgM binding to PfEMP1, we studied the PfEMP1 protein HB3VAR06, which mediates rosetting and binds IgM. Binding of IgM to this PfEMP1 involved the F-c domains C3-C4 in IgM and the penultimate DBL domain (DBL2) at the C-terminus of HB3VAR06. However, IgM binding did not inhibit specific IgG labelling of HB3VAR06 or shield IgG-opsonized IEs from phagocytosis. Instead, IgM was required for rosetting, and each pentameric IgM molecule could bind two HB3VAR06 molecules. Together, our data indicate that the primary function of F-c-mediated IgM binding in rosetting is not to shield IE from specific IgG recognition and phagocytosis as in VAR2CSA-type PfEMP1. Rather, the function appears to be strengthening of IE-erythrocyte interactions. In conclusion, our study provides new evidence on the molecular details and functional significance of rosetting, a long-recognized marker of parasites that cause severe P.falciparum malaria.
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