HNE produced by the malaria parasite Plasmodium falciparum generates HNE-protein adducts and decreases erythrocyte deformability.

In Plasmodium falciparum-parasitized erythrocytes, hemozoin (HZ) formation was accompanied by enhanced formation of 4-hydroxynonenal (HNE)-protein adducts on the cell surface, reaching in the HZ-rich schizont forms the 16.8-fold amount of control non-parasitized cells. The addition of 1-100 microM exogenous HNE to control non-parasitized cells generated HNE-adducts on surface proteins in amounts similar to those found in schizonts. Parasitized as well as HNE-treated non-parasitized erythrocytes showed decreased cell deformability (measured as decreased filterability through cylindrical-pore filters) related to the amount of HNE adducts. In vivo, the HZ-containing trophozoites and schizonts are phagocytic targets for monocytes/macrophages. The reduced deformability of circulating erythrocytes carrying HNE-adducts may increase their phagocytic elimination. Uncontrolled HNE production by parasitized erythrocytes may additionally modify non-parasitized bystander erythrocytes, induce their phagocytosis, and contribute to malarial anemia, which is predominantly due to the removal of large numbers of indirectly damaged non-parasitized erythrocytes

Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes

Publisher Correction: Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

The original version of this Article contained errors in Fig. 3. In panel a, bars from a chart depicting the percentage of antibody-positive individuals in non-infectious and infectious groups were inadvertently included in place of bars depicting the percentage of infectious individuals, as described in the Article and figure legend. However, the p values reported in the Figure and the resulting conclusions were based on the correct dataset. The corrected Fig. 3a now shows the percentage of infectious individuals in antibody-negative and -positive groups, in both the PDF and HTML versions of the Article. The incorrect and correct versions of Figure 3a are also presented for comparison in the accompanying Publisher Correction as Figure 1.The HTML version of the Article also omitted a link to Supplementary Data 6. The error has now been fixed and Supplementary Data 6 is available to download

Data from: Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes

Metadata for the protein micro-array serological analysis

Metadata for the protein microarray serological analysis. Full description of the variables provided is in tab 2 (key)

Protein microarray serological data

Background corrected and normalised microarray median florescence intensity data, for all individuals in the study (n=648). Data from IVTT protein targets are presented along with control targets in tab 1 and 2 (n=762). Data from the gametocyte IVTT protein targets only are presented in tab 3 (n=528)