Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells

Key Laboratory of Science and Technology on Microsystem, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China

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^†

These authors contributed equally to this work.

Academic Editor: Vladimir V. Yeremeev

Cells 2022, 11(3), 361; https://doi.org/10.3390/cells11030361

Received: 16 December 2021 / Revised: 15 January 2022 / Accepted: 18 January 2022 / Published: 21 January 2022

(This article belongs to the Special Issue The Immune Escape Mechanisms of Mycobacterium tuberculosis)

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Abstract

Mycobacterium tuberculosis (M. tb) is an intracellular pathogen persisting in phagosomes that has the ability to escape host immune surveillance causing tuberculosis (TB). Lipoarabinomannan (LAM), as a glycolipid, is one of the complex outermost components of the mycobacterial cell envelope and plays a critical role in modulating host responses during M. tb infection. Different species within the Mycobacterium genus exhibit distinct LAM structures and elicit diverse innate immune responses. However, little is known about the mechanisms. In this study, we first constructed a LAM-truncated mutant with fewer arabinofuranose (Araf) residues named M. sm-ΔM_6387 (Mycobacterium smegmatis arabinosyltransferase EmbC gene knockout strain). It exhibited some prominent cell wall defects, including tardiness of mycobacterial migration, loss of acid-fast staining, and increased cell wall permeability. Within alveolar epithelial cells (A549) infected by M. sm-ΔM_6387, the uptake rate was lower, phagosomes with bacterial degradation appeared, and microtubule-associated protein light chain 3 (LC3) recruitment was enhanced compared to wild type Mycobacterium smegmatis (M. smegmatis). We further confirmed that the variability in the removal capability of M. sm-ΔM_6387 resulted from host cell responses rather than the changes in the mycobacterial cell envelope. Moreover, we found that M. sm-ΔM_6387 or its glycolipid extracts significantly induced expression changes in some genes related to innate immune responses, including Toll-like receptor 2 (TLR2), class A scavenger receptor (SR-A), Rubicon, LC3, tumor necrosis factor alpha (TNF-α), Bcl-2, and Bax. Therefore, our studies suggest that nonpathogenic M. smegmatis can deposit LC3 on phagosomal membranes, and the decrease in the quantity of Araf residues for LAM molecules not only impacts mycobacterial cell wall integrity but also enhances host defense responses against the intracellular pathogens and decreases phagocytosis of host cells. View Full-Text

Keywords: Mycobacterium smegmatis; EmbC; lipoarabinomannan; LC3-associated phagocytosis; alveolar epithelial cells

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Liu, H.; Gui, X.; Chen, S.; Fu, W.; Li, X.; Xiao, T.; Hou, J.; Jiang, T. Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells. Cells 2022, 11, 361. https://doi.org/10.3390/cells11030361

AMA Style

Liu H, Gui X, Chen S, Fu W, Li X, Xiao T, Hou J, Jiang T. Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells. Cells. 2022; 11(3):361. https://doi.org/10.3390/cells11030361

Chicago/Turabian Style

Liu, Hanrui, Xuwen Gui, Shixing Chen, Weizhe Fu, Xiang Li, Tingyuan Xiao, Jie Hou, and Tao Jiang. 2022. "Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells" Cells 11, no. 3: 361. https://doi.org/10.3390/cells11030361

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Hanrui Liu

Miao J, Liu H, Qu Y, Fu W, Qi K, Zang S, Jiang T. Effect of peptidoglycan amidase MSMEG_6281 on fatty acid metabolism in Mycobacterium smegmatis. Microbial pathogenesis. 2020;140:103939.

Shixing Chen

[1] S. Chen, J. Su, Z. Zhao, Y. Shao, Y. Dou, F. Li, W. Deng, J. Shi, and Q. Li, DNA Framework-Supported Electrochemical Analysis of DNA Methylation for Prostate Cancers. 20 (2020) 7028-7035. [2] J. Miao, H. Liu, Y. Qu, W. Fu, K. Qi, S. Zang, J. He, S. Zhao, S. Chen, and T. Jiang, Effect of peptidoglycan amidase MSMEG_6281 on fatty acid metabolism in Mycobacterium smegmatis. Nano letters 140 (2020) 103939. [3] J. Ma, Rapid and Sensitive Detection of Mycobacterium tuberculosis by an Enhanced Nanobiosensor. Biosensors 6 (2021) 3367-3376. [4] Y. Yang, Z. Lu, D. Liu, Y. Wang, S. Chen, and T. Li, A Theoretical and Simulation Analysis of the Sensitivity of SiNWs-FET Sensors. 11 (2021).

Weizhe Fu

Jiajia He, Weizhe Fu, Shijia Zhao, Cuili Zhang, Tieying Sun, Tao Jiang*Lack of MSMEG_6281, a Peptidoglycan Amidase, affects Cell Wall Integrity and Virulence of Mycobacterium smegmatis.Microbial Pathogenesis, 2019,128:405-413.

Jie Hou

[1] X.D. Hou, X.Q. Guan, Y.F. Cao, Z.M. Weng, Q. Hu, H.B. Liu, S.N. Jia, S.Z. Zang, Q. Zhou, L. Yang, G.B. Ge, and J. Hou, Inhibition of pancreatic lipase by the constituents in St. John's Wort: In vitro and in silico investigations. International journal of biological macromolecules 145 (2020) 620-633. [2] X.D. Hou, L.L. Song, Y.F. Cao, Y.N. Wang, Q. Zhou, S.Q. Fang, D.C. Wu, S.Z. Zang, L. Chen, Y. Bai, G.B. Ge, and J. Hou, Pancreatic lipase inhibitory constituents from Fructus Psoraleae. Chinese journal of natural medicines 18 (2020) 369-378. [3] Q. Hu, X.Q. Guan, L.L. Song, H.N. Wang, Y. Xiong, J.L. Liu, H. Yin, Y.F. Cao, J. Hou, L. Yang, and G.B. Ge, Inhibition of pancreatic lipase by environmental xenoestrogens. Ecotoxicology and environmental safety 192 (2020) 110305. [4] N. Zheng, Y. Gu, Y. Hong, L. Sheng, L. Chen, F. Zhang, J. Hou, W. Zhang, Z. Zhang, W. Jia, and H. Li, Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid. Journal of pharmaceutical analysis 10 (2020) 560-570.

Tao Jiang

(1) Miao J, Liu H, Qu Y, Fu W, Qi K, Zang S, Jiang T. Effect of peptidoglycan amidase MSMEG_6281 on fatty acid metabolism in Mycobacterium smegmatis. Microbial pathogenesis. 2020;140:103939. (2) Huang H, Chen C, Yao F, Li X, Wang Y, Shao Y, Li X, Wang Y, Shao Y,Wang X, Zhang X, Jiang T,* and Hou L. Investigation of the Possible Role of RAD9 in Post-Diapaused Embryonic Development of the Brine Shrimp Artemiasinica. Genes(Basel). 2019;10 (10): 768 (3)Jiajia He, Weizhe Fu, Shijia Zhao, Cuili Zhang, Tieying Sun, Tao Jiang*Lack of MSMEG_6281, a Peptidoglycan Amidase, affects Cell Wall Integrity and Virulence of Mycobacterium smegmatis.Microbial Pathogenesis, 2019,128:405-413. (4) Xin Li, Jiajia He, Weizhe Fu, Pingping Cao, Siyi Zhang, Tao Jiang* Effect of Mycobacterium tuberculosis Rv3717 on cell division and cell adhesion.Microbial Pathogenesis, 2018,117:184-190. (5) JuanjuanQiu, ShizhuZang, Yufang Ma, Lawrence Owusu, Lei Zhou, Tao Jiang, Yi Xin*. Homology modeling and identification of amino acids involved in the catalytic process of Mycobacterium tuberculosis serine acetyltransferase. Molecular Medicine Reports. 2017, 15(3):1343-1347. (6) Tieying Sun, Biaojie Qin, MingchuanGao, Yuling Yin, Changyuan Wang, ShizhuZang, Xinli Li , Yi Xin and Tao Jiang* Effects of epigallocatechingallate on the cell wall structure of Mycobacterial smegmatismc2155.Natural Product Research, 2015, 29(22):2122-2124.

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Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells

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