PMID- 30029916 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20190403 IS - 1873-281X (Electronic) IS - 1472-9792 (Linking) VI - 111 DP - 2018 Jul TI - LpqT improves mycobacteria survival in macrophages by inhibiting TLR2 mediated inflammatory cytokine expression and cell apoptosis. PG - 57-66 LID - S1472-9792(18)30137-9 [pii] LID - 10.1016/j.tube.2018.05.007 [doi] AB - Tuberculosis is a severe infectious disease caused by Mycobacterium tuberculosis (Mtb). LpqT is a lipoprotein of Mtb identified as a candidate virulence factor by a high-throughput screen searching for genes important for mycobacteria intracellular survival. To investigate its function, we constructed M. smegmatis strains deficient of LpqT or overexpressing LpqT. Wildtype or LpqT modified M. smegmatis strains were used to infect macrophages and mice, and intracellular survival of mycobacteria was measured. We found that LpqT can improve M. smegmatis survival in macrophage cell line, bone marrow derived macrophages (BMDMs), and murine lungs. This survival promoting effect is dependent on TLR2 and Myd88. Western blot analysis of M. smegmatis infected macrophages showed that LpqT suppressed M. smegmatis induced NF-kappaB and MAPK phosphorylation, indicating that LpqT hampered TLR2 signal activation. In consistent with this, LpqT inhibited M. smegmatis induced inflammatory cytokine expression and cell apoptosis in macrophages, thus supported mycobacteria intracellular survival. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Li, Fengge AU - Li F AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: fengge.li@crownbio.com. FAU - Feng, Lili AU - Feng L AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: lilifeng518@163.com. FAU - Jin, Chunyan AU - Jin C AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: 20144221122@stu.suda.edu.cn. FAU - Wu, Xiaoyu AU - Wu X AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: 1810402622@qq.com. FAU - Fan, Lingbo AU - Fan L AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: flb7369@126.com. FAU - Xiong, Sidong AU - Xiong S AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: sdxiong@suda.edu.cn. FAU - Dong, Yuanshu AU - Dong Y AD - Jiangsu Key Laboratory of Infection and Immunity, Institute of Biology and Medical Sciences, Soochow University, 199 Renai Road, SIP, Suzhou, Jiangsu, China. Electronic address: ysdong@suda.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180526 PL - Scotland TA - Tuberculosis (Edinb) JT - Tuberculosis (Edinburgh, Scotland) JID - 100971555 RN - 0 (Bacterial Proteins) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipoproteins) RN - 0 (NF-kappa B) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Virulence Factors) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - *Apoptosis MH - Bacterial Proteins/genetics/*immunology/metabolism MH - Cytokines/*immunology/metabolism MH - Disease Models, Animal MH - Host-Pathogen Interactions MH - Inflammation Mediators/*immunology/metabolism MH - Lipoproteins/genetics/*immunology/metabolism MH - Macrophages/*immunology/metabolism/microbiology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microbial Viability MH - Mitogen-Activated Protein Kinases/immunology/metabolism MH - Mycobacterium Infections, Nontuberculous/*immunology/metabolism/microbiology MH - Mycobacterium smegmatis/genetics/*immunology/metabolism MH - NF-kappa B/immunology/metabolism MH - RAW 264.7 Cells MH - Signal Transduction MH - Toll-Like Receptor 2/genetics/*immunology/metabolism MH - Toll-Like Receptor 4/genetics/immunology/metabolism MH - Virulence Factors/genetics/*immunology/metabolism OTO - NOTNLM OT - Apoptosis OT - Inflammation OT - LpqT OT - Macrophage OT - Toll-like receptor OT - Tuberculosis EDAT- 2018/07/22 06:00 MHDA- 2019/04/04 06:00 CRDT- 2018/07/22 06:00 PHST- 2018/03/30 00:00 [received] PHST- 2018/05/11 00:00 [revised] PHST- 2018/05/13 00:00 [accepted] PHST- 2018/07/22 06:00 [entrez] PHST- 2018/07/22 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] AID - S1472-9792(18)30137-9 [pii] AID - 10.1016/j.tube.2018.05.007 [doi] PST - ppublish SO - Tuberculosis (Edinb). 2018 Jul;111:57-66. doi: 10.1016/j.tube.2018.05.007. Epub 2018 May 26.