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Volume 14 Issue 10
Sep.  2023
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Ruopeng Yin, Tao Wang, Huanqin Dai, Junjie Han, Jingzu Sun, Ningning Liu, Wang Dong, Jin Zhong, Hongwei Liu. Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms[J]. Protein&Cell, 2023, 14(10): 776-785. doi: 10.1093/procel/pwad016
Citation: Ruopeng Yin, Tao Wang, Huanqin Dai, Junjie Han, Jingzu Sun, Ningning Liu, Wang Dong, Jin Zhong, Hongwei Liu. Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms[J]. Protein&Cell, 2023, 14(10): 776-785. doi: 10.1093/procel/pwad016
shu

Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms

  • 1. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;

  • 2. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China;

  • 3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;

  • 4. State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China

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The work was financially supported by a grant from National Key R&D Program of China (2022YFA1304200).

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  • Received Date: February 04, 2023
  • Rev Recd Date: March 24, 2023
  • Available Online: October 23, 2023
    Graphical Abstract
    • Abstract
  • Interactions between gut microbiome and host immune system are fundamental to maintaining the intestinal mucosal barrier and homeostasis. At the host-gut microbiome interface, cell wall-derived molecules from gut commensal bacteria have been reported to play a pivotal role in training and remodeling host immune responses. In this article, we review gut bacterial cell wall-derived molecules with characterized chemical structures, including peptidoglycan and lipid-related molecules that impact host health and disease processes via regulating innate and adaptive immunity. Also, we aim to discuss the structures, immune responses, and underlying mechanisms of these immunogenic molecules. Based on current advances, we propose cell wall-derived components as important sources of medicinal agents for the treatment of infection and immune diseases.
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  • [1]
    Adam A, Petit J-F, Lefrancier P et al. Muramyl peptides:chemical structure, biological activity and mechanism of action Mol Cell Biochem 1981;41:27-47.
    [2]
    Agnihotri G, Ukani R, Malladi SS et al. Structure-activity relationships in nucleotide oligomerization domain 1 (Nod1) agonistic γ-glutamyldiaminopimelic acid derivatives J Med Chem 2011;54:1490-1510.
    [3]
    Ahmed K, Turk JL, Turk John L. Effect of anticancer agents neothramycin, aclacinomycin, FK-565 and FK-156 on the release of interleukin-2 and interleukin-1 in vitro Cancer Immunol Immunother 1989;28:87-92.
    [4]
    Alexander KL, Targan SR, Elson CO. Microbiota activation and regulation of innate and adaptive immunity Immunol Rev 2014;260:206-220.
    [5]
    Anhê FF, Barra NG, Cavallari JF et al. Metabolic endotoxemia is dictated by the type of lipopolysaccharide Cell Rep 2021;36:109691.
    [6]
    Apostolos AJ, Chordia MD, Kolli SH et al. Real-time non-invasive fluorescence imaging of gut commensal bacteria to detect dynamic changes in the microbiome of live mice Cell Chem Biol 2022;29:1721-1728.e5
    [7]
    Aron-Wisnewsky J, Warmbrunn MV, Nieuwdorp M et al. Metabolism and metabolic disorders and the microbiome:the intestinal microbiota associated with obesity, lipid metabolism, and metabolic health-pathophysiology and therapeutic strategies Gastroenterology 2021;160:573-599.
    [8]
    Bae M, Cassilly CD, Liu X et al. Akkermansia muciniphila phospholipid induces homeostatic immune responses Nature 2022;608:168-173.
    [9]
    Brown AR, Gordon RA, Hyland SN et al. Chemical biology tools for examining the bacterial cell wall Cell Chem Biol 2020;27:1052-1062.
    [10]
    Callewaert L, Michiels CW. Lysozymes in the animal kingdom J Biosci 2010;35:127-160.
    [11]
    Caruso R, Warner N, Inohara N et al. NOD1 and NOD2:signaling, host defense, and inflammatory disease Immunity 2014;41:898-908.
    [12]
    Cavallari JF, Fullerton MD, Duggan BM et al. Muramyl dipeptide-based postbiotics mitigate obesity-induced insulin resistance via IRF4 Cell Metab 2017;25:1063-1074.e3
    [13]
    Cebra JJ. Influences of microbiota on intestinal immune system development Am J Clin Nutr 1999;69:1046S1046s-1046S1051S.
    [14]
    Chamaillard M, Hashimoto M, Horie Y et al. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid Nat Immunol 2003;4:702-707.
    [15]
    Chan KL, Tam TH, Boroumand P et al. Circulating NOD1 activators and hematopoietic NOD1 contribute to metabolic inflammation and insulin resistance Cell Rep 2017;18:2415-2426.
    [16]
    Charroux B, Capo F, Kurz CL et al. Cytosolic and secreted peptidoglycan-degrading enzymes in drosophila respectively control local and systemic immune responses to microbiota Cell Host Microbe 2018;23:215-228.e4.
    [17]
    Chatzidaki-Livanis M, Weinacht KG, Comstock LE. Trans locus inhibitors limit concomitant polysaccharide synthesis in the human gut symbiont Bacteroides fragilis Proc Natl Acad Sci USA 2010;107:11976-11980.
    [18]
    Chen J, Xiao Y, Li D et al. New insights into the mechanisms of high-fat diet mediated gut microbiota in chronic diseases iMeta 2023;2:e69.
    [19]
    Choi S-C, Brown J, Gong M et al. Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice Sci Transl Med 2020;12:eaax2220.
    [20]
    d'Hennezel E, Abubucker S, Murphy LO et al. Total lipopolysaccharide from the human gut microbiome silences toll-like receptor signaling mSystems 2017;2:e00046-e00017.
    [21]
    Di Lorenzo F, De Castro C, Silipo A et al. Lipopolysaccharide structures of Gram-negative populations in the gut microbiota and effects on host interactions FEMS Microbiol Rev 2019;43:257-272.
    [22]
    Di Lorenzo F, Pither MD, Martufi M et al. Pairing Bacteroides vulgatus LPS structure with its immunomodulatory effects on human cellular models ACS Cent Sci 2020;6:1602-1616.
    [23]
    Durant L, Stentz R, Noble A et al. Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease Microbiome 2020;8:88.
    [24]
    Dvorožňáková E, Porubcová J, Šnábel V et al. Imunomodulative effect of liposomized muramyltripeptide phosphatidylethanolamine (L-MTP-PE) on mice with alveolar echinococcosis and treated with albendazole Parasitol Res 2008;103:919-929.
    [25]
    Dworkin J. The medium is the message:interspecies and interkingdom signaling by peptidoglycan and related bacterial glycans Annu Rev Microbiol 2014;68:137-154.
    [26]
    Egan AJF, Errington J, Vollmer W. Regulation of peptidoglycan synthesis and remodelling Nat Rev Microbiol 2020;18:446-460.
    [27]
    Erturk-Hasdemir D, Oh SF, Okan NA et al. Symbionts exploit complex signaling to educate the immune system Proc Natl Acad Sci USA 2019;116:26157-26166.
    [28]
    Fernandez EM, Valenti V, Rockel C et al. Anti-inflammatory capacity of selected Lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide Gut 2011;60:1050-1059.
    [29]
    Friedrich AD, Campo VE, Cela EM et al. Oral administration of lipoteichoic acid from Lactobacillus rhamnosus GG overcomes UVB-induced immunosuppression and impairs skin tumor growth in mice Eur J Immunol 2019;49:2095-2102.
    [30]
    Gabanyi I, Lepousez G, Wheeler R et al. Bacterial sensing via neuronal Nod2 regulates appetite and body temperature Science 2022;376:eabj3986.
    [31]
    Gao J, Zhao X, Hu S et al. Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway Cell Host Microbe 2022;30:1435-1449.e9.
    [32]
    Geng S, Li Q, Zhou X et al. Gut commensal E. coli outer membrane proteins activate the host food digestive system through neural-immune communication Cell Host Microbe 2022;30:1401-1416.e8.
    [33]
    Girardin SE, Boneca IG, Carneiro LAM et al. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan Science 2003;300:1584-1587.
    [34]
    Griffin ME, Espinosa J, Becker JL et al. Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy Science 2021;373:1040-1046.
    [35]
    Heimesaat MM, Fischer A, Jahn H-K et al. Exacerbation of murine ileitis by Toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal Escherichia coli Gut 2007;56:941-948.
    [36]
    Hoffmann JA, Kafatos FC, Janeway CA et al. Phylogenetic perspectives in innate immunity Science 1999;284:1313-1318.
    [37]
    Hou K, Wu Z-X, Chen X-Y et al. Microbiota in health and diseases Sig Transduct Target Ther 2022;7:135.
    [38]
    Huang Z, Wang J, Xu X et al. Antibody neutralization of microbiota-derived circulating peptidoglycan dampens inflammation and ameliorates autoimmunity Nat Microbiol 2019;4:766-773.
    [39]
    Ivanov II, McKenzie BS, Zhou L et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells Cell 2006;126:1121-1133.
    [40]
    Ivanov II, Rosa de Frutos L, Manel N et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine Cell Host Microbe 2008;4:337-349.
    [41]
    Jacobs JP, Goudarzi M, Singh N et al. A disease-associated microbial and metabolomics state in relatives of pediatric inflammatory bowel disease patients Cell Mol Gastroenterol Hepatol 2016;2:750-766.
    [42]
    Jiang S, Chen D, Ma C et al. Establishing a novel inflammatory bowel disease prediction model based on gene markers identified from single nucleotide variants of the intestinal microbiota iMeta 2022;1.
    [43]
    Kim B, Wang Y-C, Hespen CW et al. Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis eLife 2019;8:e45343.
    [44]
    Kojima N, Kojima S, Hosokawa S et al. Wall teichoic acid-dependent phagocytosis of intact cell walls of Lactiplantibacillus plantarum elicits IL-12 secretion from macrophages Front Microbiol 2022;13:986396.
    [45]
    Krautkramer KA, Fan J, Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates Nat Rev Microbiol 2021;19:77-94.
    [46]
    Kurokawa K, Jung D-J, An J-H et al. Glycoepitopes of Staphylococcal wall teichoic acid govern complement-mediated opsonophagocytosis via human serum antibody and mannose-binding lectin J Biol Chem 2013;288:30956-30968.
    [47]
    Lai H-C, Lin T-L, Chen T-W et al. Gut microbiota modulates COPD pathogenesis:role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide Gut 2022;71:309-321.
    [48]
    Li Y, Wang Y, Shi F et al. Phospholipid metabolites of the gut microbiota promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells Gut Microbes 2022;14:2096994.
    [49]
    Lin D, Gao Y, Zhao L et al. Enterococcus faecalis lipoteichoic acid regulates macrophages autophagy via PI3K/Akt/mTOR pathway Biochem Biophys Res Commun 2018;498:1028-1036.
    [50]
    Liu S, Zhao W, Lan P et al. The microbiome in inflammatory bowel diseases:from pathogenesis to therapy Protein Cell 2021;12:331-345.
    [51]
    Maisonneuve C, Tsang DKL, Foerster EG et al. Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells Cell Rep 2021;34:108677.
    [52]
    Mallott EK, Amato KR. Host specificity of the gut microbiome Nat Rev Microbiol 2021;19:639-653.
    [53]
    Matsuzaki C, Shiraishi T, Chiou T-Y et al. Role of lipoteichoic acid from the genus Apilactobacillus in inducing a strong IgA response Appl Environ Microbiol 2022;88:e00190-e00122.
    [54]
    Mondragón-Palomino O, Poceviciute R, Lignell A et al. Three-dimensional imaging for the quantification of spatial patterns in microbiota of the intestinal mucosa Proc Natl Acad Sci USA 2022;119:e2118483119.
    [55]
    Monnot GC, Wegrecki M, Cheng T-Y et al. Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a Nat Immunol 2023;24:110-122.
    [56]
    Nenci A, Becker C, Wullaert A et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation Nature 2007;446:557-561.
    [57]
    Nigro G, Rossi R, Commere P-H et al. The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration Cell Host Microbe 2014;15:792-798.
    [58]
    Ohya Y, Nishimoto T, Ouchi T. Design of d-glucose analogue of MDP/CM-curdlan conjugate and its immunological enhancement activity Carbohydr Polym 1993;20:43-49.
    [59]
    Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity Immunol Rev 2009;227:221-233.
    [60]
    Pan Q, Guo F, Huang Y et al. Gut microbiota dysbiosis in systemic lupus erythematosus:novel insights into mechanisms and promising therapeutic strategies Front Immunol 2021;12:799788.
    [61]
    Pedicord VA, Lockhart AAK, Rangan KJ et al. Exploiting a host-commensal interaction to promote intestinal barrier function and enteric pathogen tolerance Sci Immunol 2016;1.
    [62]
    Plovier H, Everard A, Druart C et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice Nat Med 2017;23:107-113.
    [63]
    Ramakrishna C, Kujawski M, Chu H et al. Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis Nat Commun 2019;10:2153.
    [64]
    Rangan KJ, Pedicord VA, Wang Y-C et al. A secreted bacterial peptidoglycan hydrolase enhances tolerance to enteric pathogens Science 2016;353:1434-1437.
    [65]
    Rathinam VAK, Zhao Y, Shao F. Innate immunity to intracellular LPS Nat Immunol 2019;20:527-533.
    [66]
    Riehl TE, Alvarado D, Ee X et al. Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells Gut 2019;68:1003-1013.
    [67]
    Schroeder BO, Bäckhed F. Signals from the gut microbiota to distant organs in physiology and disease Nat Med 2016;22:1079-1089.
    [68]
    Schwarzer M, Gautam UK, Makki K et al. Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice Science 2023;379:826-833.
    [69]
    Shahine A, Reinink P, Reijneveld JF et al. A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids Nat Commun 2019;10:56.
    [70]
    Shida K, Kiyoshima-Shibata J, Kaji R et al. Peptidoglycan from Lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms Immunology 2009;128:e858-e869.
    [71]
    Shiraishi T, Yokota S, Fukiya S et al. Structural diversity and biological significance of lipoteichoic acid in Gram-positive bacteria:focusing on beneficial probiotic lactic acid bacteria Biosci Microbiota Food Health 2016;35:147-161.
    [72]
    Smith, PM, Howitt, MR, Panikov, N et al. The microbial metabolites, short-chain fatty acids, regulate colonic T reg cell homeostasis Science 2013;341:569-573.
    [73]
    Spindler MP, Siu S, Mogno I et al. Human gut microbiota stimulate defined innate immune responses that vary from phylum to strain Cell Host Microbe 2022;30:1481-1498.e5.
    [74]
    Stafford CA, Gassauer A-M, de Oliveira Mann CC et al. Phosphorylation of muramyl peptides by NAGK is required for NOD2 activation Nature 2022;609:590-596.
    [75]
    Steimle A, Michaelis L, Di Lorenzo F et al. Weak agonistic LPS restores intestinal immune homeostasis Mol Ther 2019;27:1974-1991.
    [76]
    Sun D, Bai R, Zhou W et al. Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae Gut 2021;70:666-676.
    [77]
    Sun H, Guo Y, Wang H et al. Gut commensal Parabacteroides distasonis alleviates inflammatory arthritis Gut 2023;2022:327756.
    [78]
    Tei R, Baskin JM. Click chemistry and optogenetic approaches to visualize and manipulate phosphatidic acid signaling J Biol Chem 2022;298:101810.
    [79]
    Teng F, Klinger CN, Felix KM et al. Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of peyer's patch T follicular helper cells Immunity 2016;44:875-888.
    [80]
    Tian D, Han M Bacterial peptidoglycan muropeptides benefit mitochondrial homeostasis and animal physiology by acting as ATP synthase agonists Develop Cell 2022;57:361-372.e5.
    [81]
    Typas A, Banzhaf M, Gross CA et al. From the regulation of peptidoglycan synthesis to bacterial growth and morphology Nat Rev Microbiol 2012;10:123-136.
    [82]
    Van Rhijn I, van Berlo T, Hilmenyuk T et al. Human autoreactive T cells recognize CD1b and phospholipids Proc Natl Acad Sci USA 2016;113:380-385.
    [83]
    Vollmer W, Blanot D, De Pedro MA. Peptidoglycan structure and architecture FEMS Microbiol Rev 2008a;32:149-167.
    [84]
    Vollmer W, Joris B, Charlier P et al. Bacterial peptidoglycan (murein) hydrolases FEMS Microbiol Rev 2008b;32:259-286.
    [85]
    de Vos WM, Tilg H, Van Hul M et al. Gut microbiome and health:mechanistic insights Gut 2022;71:1020-1032.
    [86]
    Wang S, Heng BC, Qiu S et al. Lipoteichoic acid of Enterococcus faecalis inhibits osteoclastogenesis via transcription factor RBP-J Innate Immun 2019;25:13-21.
    [87]
    Wang L, Tang L, Feng Y et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8 + T cells in mice Gut 2020a;69:1988-1997.
    [88]
    Wang S, Ahmadi S, Nagpal R et al. Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions:from C. elegans to mice GeroScience 2020b;42:333-352.
    [89]
    Wang W, Yang Q, Du Y et al. Metabolic labeling of peptidoglycan with NIR-II Dye enables in vivo imaging of gut microbiota Angew Chem Int Ed 2020c;59:2628-2633.
    [90]
    Weaver CT, Elson CO, Fouser LA et al. The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin Annu Rev Pathol Mech Dis 2013;8:477477512.
    [91]
    Whitney JC, Peterson SB, Kim J et al. A broadly distributed toxin family mediates contact-dependent antagonism between Gram-positive bacteria eLife 2017;6:e26938.
    [92]
    Willis LM, Stupak J, Richards MR et al. Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens Proc Natl Acad Sci USA 2013;110:7868-7873.
    [93]
    Wolf AJ, Reyes CN, Liang W et al. Hexokinase is an innate immune receptor for the detection of bacterial peptidoglycan Cell 2016;166:624-636.
    [94]
    Wu J, Wang K, Wang X et al. The role of the gut microbiome and its metabolites in metabolic diseases Protein Cell 2021;12:360-373.
    [95]
    Yang W, Cong Y. Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases Cell Mol Immunol 2021;18:866-877.
    [96]
    Yu J, Xiao K, Chen X et al. Neuron-derived neuropeptide Y fine-tunes the splenic immune responses Neuron 2022;110:1327-1339.e6.
    [97]
    Zhang H, Liao X, Sparks JB et al. Dynamics of gut microbiota in autoimmune lupus Appl Environ Microbiol 2014;80:7551-7560.
    [98]
    Zou Y, Xue W, Luo G et al. 1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses Nat Biotechnol 2019;37:179-185.
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