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Genome-Wide Expression Analysis of Placental Malaria Reveals Features of Lymphoid Neogenesis during Chronic

Summary: Genome-Wide Expression Analysis of Placental Malaria
Reveals Features of Lymphoid Neogenesis during Chronic
Atis Muehlenbachs,*
Michal Fried,*
Jeff Lachowitzer,* Theonest K. Mutabingwa,*งถ
and Patrick E. Duffy2
Chronic inflammation during placental malaria (PM) is most frequent in first time mothers and is associated with poor
maternal and fetal outcomes. In the first genome-wide analysis of the local human response to sequestered malaria parasites,
we identified genes associated with chronic PM and then localized the corresponding proteins and immune cell subsets in
placental cryosections. B cell-related genes were among the most highly up-regulated transcripts in inflamed tissue. The B
cell chemoattractant CXCL13 was up-regulated >1,000-fold, and B cell-activating factor was also detected. Both proteins
were expressed by intervillous macrophages. Ig L and H chain transcription increased significantly, and heavy depositions
of IgG3 and IgM were observed in intervillous spaces. The B cell phenotype was heterogenous, including naive (CD27-
negative), mature (CD138-positive), and cycling (Ki-67-positive) cells. B cells expressed T-bet but not Bcl-6, suggesting T
cell-independent activation without germinal center formation. Genes for the Fc binding proteins Fc RIa, Fc RIIIa, and
C1q were highly up-regulated, and the proteins localized to intervillous macrophages. Birth weight was inversely correlated
with transcript levels of CXCL13, IgG H chain, and IgM H chain. The iron regulatory peptide hepcidin was also expressed
but was not associated with maternal anemia. The results suggest that B cells and macrophages contribute to chronic PM


Source: Arnold, Jonathan - Nanoscale Science and Engineering Center & Department of Genetics, University of Georgia


Collections: Biotechnology