title: Guanylate-binding protein 1 (GBP1) contributes to the immunity of human mesenchymal stromal cells against Toxoplasma gondii.
abstract: Mesenchymal stromal cells (MSCs) have recently been shown to play important roles in mammalian host defenses against intracellular pathogens, but the molecular mechanism still needs to be clarified. We confirmed that human MSCs (hMSCs) prestimulated with IFN-γ showed a significant and dose-dependent ability to inhibit the growth of two types of Toxoplasma gondii [type I RH strain with green fluorescent proteins (RH/GFP) or type II PLK strain with red fluorescent proteins (PLK/RED)]. However, in contrast to previous reports, the anti-T. gondii activity of hMSCs was not mediated by indoleamine 2,3-dioxygenase (IDO). Genome-wide RNA sequencing (RNA-seq) analysis revealed that IFN-γ increased the expression of the p65 family of human guanylate-binding proteins (hGBPs) in hMSCs, especially hGBP1. To analyze the functional role of hGBPs, stable knockdowns of hGBP1, -2, and -5 in hMSCs were established using a lentiviral transfection system. hGBP1 knockdown in hMSCs resulted in a significant loss of the anti-T. gondii host defense property, compared with hMSCs infected with nontargeted control sequences. hGBP2 and -5 knockdowns had no effect. Moreover, the hGBP1 accumulation on the parasitophorous vacuole (PV) membranes of IFN-γ-stimulated hMSCs might protect against T. gondii infection. Taken together, our results suggest that hGBP1 plays a pivotal role in anti-T. gondii protection of hMSCs and may shed new light on clarifying the mechanism of host defense properties of hMSCs.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Qin
authors.affiliation: Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: De-Hua
authors.identifier: 0000-0002-4709-1507
authors.initials: DH
authors.lastname: Lai
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.|Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wu
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.|Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.|Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Sunxing
authors.initials: S
authors.lastname: Yan
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
authors.affiliation: Ecosystems and Environment Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, United Kingdom.|Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, United Kingdom.
authors.forename: Geoff
authors.initials: G
authors.lastname: Hide
authors.affiliation: Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China; fjayala@uci.edu lsslzr@mail.sysu.edu.cn xiangp@mail.sysu.edu.cn.|Ecosystems and Environment Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, United Kingdom.|Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, United Kingdom.
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697; fjayala@uci.edu lsslzr@mail.sysu.edu.cn xiangp@mail.sysu.edu.cn.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ayala
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; fjayala@uci.edu lsslzr@mail.sysu.edu.cn xiangp@mail.sysu.edu.cn.|Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006367:HeLa Cells; D006790:Host-Parasite Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D034622:RNA Interference; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014617:Vacuoles / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology
chemical_list: C490287:GBP1 protein, human; D008164:Luminescent Proteins; D007371:Interferon-gamma; D019204:GTP-Binding Proteins
keywords: human stem cells; in vitro cultivation; innate immunity; parasitic protozoan