Blood donor variability is a modulatory factor for P. falciparum invasion phenotyping assays
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Scientific Reports
Abstract
Human erythrocytes are indispensable for Plasmodium falciparum development. Unlike other
eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum
in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of
diferent individuals. However, the contribution of the erythrocytes variation in infuencing invasion
rates remains unknown, which represents a challenge for conducting large-scale comparative studies.
Here, we used erythrocytes of diferent blood groups harboring diferent hemoglobin genotypes
to assess the relative contribution of blood donor variability in P. falciparum invasion phenotyping
assays. For each donor, we investigated the relationship between parasite invasion phenotypes and
erythrocyte phenotypic characteristics, including the expression levels of surface receptors (e.g. the
human glycophorins A and C, the complement receptor 1 and decay accelerating factor), blood groups
(e.g. ABO/Rh system), and hemoglobin genotypes (e.g. AA, AS and AC). Across all donors, there were
signifcant diferences in invasion efciency following treatment with either neuraminidase, trypsin
or chymotrypsin relative to the control erythrocytes. Primarily, we showed that the levels of key
erythrocyte surface receptors and their sensitivity to enzyme treatment signifcantly difered across
donors. However, invasion efciency did not correlate with susceptibility to enzyme treatment or
with the levels of the selected erythrocyte surface receptors. Furthermore, we found no relationship
between P. falciparum invasion phenotype and blood group or hemoglobin genotype. Altogether, our
fndings demonstrate the need to consider erythrocyte donor uniformity and anticipate challenges
associated with blood donor variability in early stages of large-scale study design.
Description
Keywords
Blood donor variability, modulatory factor, falciparum invasion, phenotyping, assays