Individual mean fluorescence intensities (MFI) are shown in a box plot extending from the 25th to the 75th percentiles with a line at the median
Individual mean fluorescence intensities (MFI) are shown in a box plot extending from the 25th to the 75th percentiles with a line at the median. and Q3) of observed concentration fold changes across all antigens tested is listed, showing a similar and general change in IgG responses to all antigens for each volunteer. To the right, the percentage of antigens within each group, which were considered outliers, is shown, indicating antigens to which increased IgG reactivity was considered antigen-specific, as the increase in IgG reactivity was above 1.5x the interquartile range. Day 28 IgG was from volunteer L1-025 was not analyzed.(DOCX) ppat.1007906.s005.docx (27K) GUID:?E40E7270-EB0D-4CCA-9688-8CBDE1D985C3 S6 Table: Primer sets used for qPCR analysis. (DOCX) ppat.1007906.s006.docx (36K) GUID:?E7BB57EC-876F-4B7D-87FD-72729FCF9EA1 S1 Fig: Volunteer antibody response against individual CIDR domains and controls prior to infection (day -1). Heat map showing reactivity of patient plasma samples prior to contamination with gene expression, luminex data and contamination curves of the volunteers. The first two model components summarized 33% and 21% of the data variance, respectively, highlighting high diversity in the underlying data structure. The biplot shows that controller and non-controller cluster along the first two principal components. They can be separated along the first principal component and controller also tend to have lower scores on component 2. However, participant L1-026 (a controller’) has the highest score on component 2, which SSE15206 is usually primarily due to an individual gene expression pattern.(PDF) ppat.1007906.s009.pdf (19K) GUID:?46C42619-4DCC-48BD-AE0F-B7658B8DA8CD S4 Fig: Correlation analysis of samples from two serial parasite generations obtained from volunteers L1-006, L1-010, L1-017 and L1-019. samples from two consecutive parasite generations could be obtained from four volunteers. L1-006, L1-017 and L1-019 belong to the group of non-controller, L1-010 to the controller group. Expression data were normalized on total expression in each sample (%) and Spearmans rank correlation coefficients (gene expression across the parasite replication cycles analyzed. Day of sampling is usually indicated as day post contamination. genes color-coded consistently with the main figures: red (group A), orange (subfamily decrease and increase over time in volunteer L1-026 determined by qPCR. RELATEXP values for and normalized against the housekeeping gene and in samples from the different volunteer groups. No difference in median expression was observed for all those primer sets between the volunteer groups malaria-na?ve, non-controller and controller in regard of RNA content in the samples. Data are shown in box plots extending from the 25th to the 75th percentiles with a line at the median.(PDF) ppat.1007906.s012.pdf (41K) GUID:?EB8651E1-9A1A-49D9-A67C-0105E7F64F7A Data Availability StatementAll relevant data are within the manuscript and its Supporting Information files. Abstract The pathogenesis of SSE15206 malaria is usually linked to the variant surface antigen genes per parasite genome. Repeated episodes of malaria contamination result in the gradual acquisition of protective antibodies against models there is only limited experimental evidence in support of this concept. To get insight into the impact of naturally acquired immunity around the expressed gene repertoire early during contamination we performed controlled human malaria infections of 20 adult African volunteers with life-long malaria exposure using SSE15206 aseptic, purified, cryopreserved sporozoites (Sanaria PfSPZ Challenge) and correlated serological data with gene expression patterns from parasites. Among the 10 African volunteers who developed patent infections, Rabbit polyclonal to ADNP individuals with low antibody levels SSE15206 showed a steep rise in parasitemia accompanied by broad activation of multiple, predominantly subtelomeric genes, comparable to what we previously observed in na?ve volunteers. In contrast, individuals with intermediate antibody levels developed asymptomatic infections and the parasite populations expressed only few gene variants, indicative of clonal selection. Importantly, in contrast to parasites from na?ve volunteers, expression of genes coding for endothelial protein C receptor (EPCR)-binding gene expression for up to six parasite replication cycles and demonstrated for the first time a shift in the dominant gene variant. In conclusion, our data suggest that activates multiple subtelomeric genes at the onset of blood stage contamination facilitating rapid growth of parasite clones which express are responsible for the most severe form of malaria, particularly affecting children under the age of five years, and escape from the human immune response by antigenic variation. This is achieved by alteration of the host cell surface exposed protein gene expression remains essential to understanding pathogenesis and immunity in humans. We can show that at the onset of the blood stage in malaria-na?ve hosts the parasite population activates a large group of.