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It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms driving MC activation, however, are incompletely understood. We sought to understand whether immunoglobulin E (IgE), a potent activator of MCs, was associated with KS incidence and severity. In a cross-sectional study of untreated human immunodeficiency virus (HIV)-infected adults with or without KS in Uganda, we found that patients with KS had higher plasma IgE levels than those without KS. After adjustment for age, sex, CD4+ T-cell count, and HIV RNA levels, there was a dose-response relationship between plasma IgE levels and the presence and severity of KS. Higher eosinophil counts were also associated with IgE levels, and plasma interleukin 33 concentrations were higher in individuals with KS. These findings suggest that IgE-driven atopic inflammation may contribute the pathogenesis of KS. Therapies targeting IgE-mediated MC activation thus might represent a novel approach for treatment or prevention of KS.

Macrophages are important target cells for diverse viruses and thus represent a valuable system for studying virus biology. Isolation of primary human macrophages is done by culture of dissociated tissues or from differentiated blood monocytes, but these methods are both time consuming and result in low numbers of recovered macrophages. Here, we explore whether macrophages derived from human induced pluripotent stem cells (iPSCs)--which proliferate indefinitely and potentially provide unlimited starting material--could serve as a faithful model system for studying virus biology. Human iPSC-derived monocytes were differentiated into macrophages and then infected with HIV-1, dengue virus, or influenza virus as model human viruses. We show that iPSC-derived macrophages support the replication of these viruses with kinetics and phenotypes similar to human blood monocyte-derived macrophages. These iPSC-derived macrophages were virtually indistinguishable from human blood monocyte-derived macrophages based on surface marker expression (flow cytometry), transcriptomics (RNA sequencing), and chromatin accessibility profiling. iPSC lines were additionally generated from non-human primate (chimpanzee) fibroblasts. When challenged with dengue virus, human and chimpanzee iPSC-derived macrophages show differential susceptibility to infection, thus providing a valuable resource for studying the species-tropism of viruses. We also show that blood- and iPSC-derived macrophages both restrict influenza virus at a late stage of the virus lifecycle. Collectively, our results substantiate iPSC-derived macrophages as an alternative to blood monocyte-derived macrophages for the study of virus biology. [ABSTRACT FROM AUTHOR]