Friday, 06 October 2017 16:25

Malaria receptor plays role in red blood cell invasion

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Published in mBiosphere

Plasmodium falciparum, which causes malaria in people, resides in red blood cells (also called erythrocytes) of infected individuals. How does it first get inside its host cell? Are there preferred entry pathways, and if so, how does the pathogen rank them? These are questions addressed by first author Selasi Dankwa and senior scientist Manoj Duraisingh in their recently published Infection and Immunity article.

 

IAIJournal: Genetic evidence for erythrocyte receptor glycophorin B expression levels defining a dominant Plasmodium falciparum invasion pathway in to human erythrocytes.

Because getting inside the red blood cells is such an important step in the malaria infection cycle, there are a number of pathogen receptors for different cell ligands, and some of these receptor-ligand interactions are well characterized. Other interactions, such as that between P. falciparum Erythrocyte Binding-Like 1 (EBL-1) and red blood cell glycophorin B (GPB), are less understood. The authors investigated this interaction by genetic knockdown of the erythrocyte glycophorin receptors to better characterize the GPB role during invasion. 

2017.10.6 MalariaTable summarizing invasion efficiency in different genetic knockdown cell lines relative to controls. Source.

The scientists first generated individual knockdown of one of three glycophorin proteins GPA, GPB, and GPC in hematopoetic stem cell precursors, decreasing the surface protein levels by at least 80%. These cell lines were differentiated into erythrocytes and tested for P. falciparum invasion using both lab-adapted strains and field isolates. Both types of P. falciparum showed less cell invasion when the red blood cells expressed lower levels of GPB, and in some cases, GPB knockdown inhibited invasion more than knockdown of either GPA or GPC, two additional glycophorin proteins that act as malaria receptor ligands (see table, right). This suggests that some strains use GPB preferentially to enter their host cells.

Understanding the hierarchy of invasion mechanisms used by malaria strains can lead to more effective treatments to block invasion. In all strains, knockdown of GPC conferred the least invasion defects, suggesting this receptor is not the preferred entry pathway and blocking this receptor will not prevent malaria infections. A more effective strategy would be to concentrate on blocking GPA and GPB interactions with their cell ligands, perhaps by screening for natural invasion-inhibitory antibodies, as found for other malaria receptors, in malaria-endemic areas.

The authors also analyzed a previously published set of transcriptome data from malaria-infected and otherwise healthy children from Benin in West Africa, to better understand this host-microbial interaction. They found that glycophorin B transcript levels vary more widely in healthy children than most erythroid cell-specific transcripts [Aside: do red blood cells, which lose their nucleus during differentiation, have transcripts? Indeed they do.]. These expression level differences may have been selected for in populations exposed to malaria for many generations, suggest the authors, but further studies are needed to confirm and understand the significance of this variation.

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Last modified on Friday, 06 October 2017 16:52
Julie Wolf

ASM Communications Social Media Specialist Julie Wolf spent her research career focused on medical mycology and infectious disease. Broadly interested in microbiology and scientific communication, she has taught at Long Island University and the community biolab Genspace and has written for the Scientista Foundation and Scholastic’s Science World magazine. Follow her on Twitter for more ASM and Microbiology highlights at @JulieMarieWolf.

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