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Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-Seq
Liang Cheng, … , Xiao-Ning Xu, Lishan Su
Liang Cheng, … , Xiao-Ning Xu, Lishan Su
Published May 14, 2020
Citation Information: JCI Insight. 2020;5(11):e135344. https://doi.org/10.1172/jci.insight.135344.
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Resource and Technical Advance AIDS/HIV

Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-Seq

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Abstract

Depletion of CD4+ T cells during HIV-1 infection is mostly mediated by inflammatory cells via indirect but not clearly defined mechanisms. In this report, we used single-cell RNA-Seq (scRNA-Seq) technology to study HIV-induced transcriptomic change in innate immune cells in lymphoid organs. We performed scRNA-Seq on hCD45+hCD3–hCD19– human leukocytes isolated from spleens of humanized NOD/Rag2–/–γc–/– (NRG) mice transplanted with human CD34+ hematopoietic stem progenitor cells (NRG-hu HSC mice). We identified major populations of innate immune cells, including plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), macrophages, NK cells, and innate lymphoid cells (ILCs). HIV-1 infection significantly upregulated genes involved in type I IFN inflammatory pathways in each of the innate immune subsets. Interestingly, we found that TRAIL was upregulated in the innate immune populations, including pDCs, mDCs, macrophages, NK cells, and ILCs. We further demonstrated that blockade of the TRAIL signaling pathway in NRG-hu HSC mice prevented HIV-1–induced CD4+ T cell depletion in vivo. In summary, we characterized HIV-induced transcriptomic changes of innate immune cells in the spleen at single-cell levels, identified the TRAIL+ innate immune cells, and defined an important role of the TRAIL signaling pathway in HIV-1–induced CD4+ T cell depletion in vivo.

Authors

Liang Cheng, Haisheng Yu, John A. Wrobel, Guangming Li, Peng Liu, Zhiyuan Hu, Xiao-Ning Xu, Lishan Su

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Figure 1

scRNA-Seq analysis of human CD45+CD3–CD19– immune cells in spleens of NRG-hu HSC mice.

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scRNA-Seq analysis of human CD45+CD3–CD19– immune cells in spleens of NR...
(A) t-SNE analysis of hCD45+hCD3–hCD19– splenocyte clusters from NRG-hu HSC mice based on 6023 single-cell transcriptomes. Cell counts for plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC), macrophages, NK cells (NK), innate lymphoid cells (ILC), IDO+ myeloid cells, mast cells, CD34+ progenitor cells, B cells, and erythroid cells are indicated in parentheses. (B) Violin plots showing expression of representative marker genes for each cell type cluster. (C) Heatmap of marker gene expression in individual cells of each cell type cluster.

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