Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-seq
| Autor: | Haisheng Yu, John A Wrobel, Xiao-Ning Xu, Zhiyuan Hu, Peng Liu, Lishan Su, Guangming Li, Liang Cheng |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Myeloid CD34 HIV Infections Spleen Biology TNF-Related Apoptosis-Inducing Ligand Mice 03 medical and health sciences 0302 clinical medicine Mice Inbred NOD medicine Animals Humans RNA-Seq Progenitor cell Mice Knockout Innate immune system Innate lymphoid cell General Medicine Immunity Innate Haematopoiesis 030104 developmental biology Lymphatic system medicine.anatomical_structure Gene Expression Regulation Technical Advance 030220 oncology & carcinogenesis Immunology HIV-1 Leukocytes Mononuclear Signal Transduction |
| Zdroj: | JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | 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(–/–)γ(c)(–/–) (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. |
| Databáze: | OpenAIRE |
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