PMID- 36315280 OWN - NLM STAT- MEDLINE DCOM- 20230209 LR - 20230209 IS - 1420-908X (Electronic) IS - 1023-3830 (Print) IS - 1023-3830 (Linking) VI - 72 IP - 1 DP - 2023 Jan TI - Viperin deficiency promotes dendritic cell activation and function via NF-kappaB activation during Mycobacterium tuberculosis infection. PG - 27-41 LID - 10.1007/s00011-022-01638-3 [doi] AB - OBJECTIVES AND DESIGN: Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. METHODS: We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. RESULTS: Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4(+) and CD8(+) T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-kappaB p65 activation. NF-kappaB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. CONCLUSIONS: These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy. CI - (c) 2022. The Author(s). FAU - Zhou, Xinying AU - Zhou X AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. zxyforever@smu.edu.cn. FAU - Xu, Hui AU - Xu H AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Li, Qianna AU - Li Q AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Wang, Qi AU - Wang Q AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Liu, Honglin AU - Liu H AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Huang, Yingqi AU - Huang Y AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Liang, Yao AU - Liang Y AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Lie, Linmiao AU - Lie L AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Han, Zhenyu AU - Han Z AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Chen, Yaoxin AU - Chen Y AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Huang, Yulan AU - Huang Y AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Zhou, Wenle AU - Zhou W AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Wen, Qian AU - Wen Q AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Zhou, Chaoying AU - Zhou C AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Hu, Shengfeng AU - Hu S AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. FAU - Ma, Li AU - Ma L AD - Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China. mali_61648322@smu.edu.cn. LA - eng GR - 82070010/National Natural Science Foundation of China/ GR - 82072242/National Natural Science Foundation of China/ GR - 2019A1515010988/Guangdong Basic and Applied Basic Research Foundation/ GR - 2021A1515010933/Guangdong Basic and Applied Basic Research Foundation/ PT - Journal Article DEP - 20221031 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Viperin Protein) SB - IM MH - Chemokines/metabolism MH - Cytokines MH - Dendritic Cells MH - *Mycobacterium tuberculosis/metabolism MH - NF-kappa B/metabolism MH - *Tuberculosis MH - *Viperin Protein/metabolism MH - Animals PMC - PMC9902321 OTO - NOTNLM OT - Dendritic cells (DCs) OT - Immune responses OT - Mycobacterium tuberculosis (Mtb) OT - NF-kappaB OT - Viperin COIS- The authors declare no competing interests. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/11/01 06:00 MHDA- 2023/02/09 06:00 PMCR- 2022/10/31 CRDT- 2022/10/31 12:14 PHST- 2022/05/16 00:00 [received] PHST- 2022/09/01 00:00 [accepted] PHST- 2022/08/30 00:00 [revised] PHST- 2022/11/01 06:00 [pubmed] PHST- 2023/02/09 06:00 [medline] PHST- 2022/10/31 12:14 [entrez] PHST- 2022/10/31 00:00 [pmc-release] AID - 10.1007/s00011-022-01638-3 [pii] AID - 1638 [pii] AID - 10.1007/s00011-022-01638-3 [doi] PST - ppublish SO - Inflamm Res. 2023 Jan;72(1):27-41. doi: 10.1007/s00011-022-01638-3. Epub 2022 Oct 31.