A screen of Crohn's disease-associated microbial metabolites identifies ascorbate as a novel metabolic inhibitor of activated human T cells.
Apoptosis
Ascorbic Acid
/ metabolism
Cell Differentiation
Cell Respiration
Cells, Cultured
Crohn Disease
/ immunology
Energy Metabolism
Humans
Interferon-gamma
/ metabolism
Interleukin-17
/ metabolism
Interleukin-4
/ metabolism
Lymphocyte Activation
Mass Screening
Microbiota
/ immunology
Th17 Cells
/ immunology
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
01
05
2017
accepted:
27
02
2018
revised:
17
01
2018
pubmed:
27
4
2018
medline:
25
6
2019
entrez:
27
4
2018
Statut:
ppublish
Résumé
Microbial metabolites are an emerging class of mediators influencing CD4
Identifiants
pubmed: 29695840
doi: 10.1038/s41385-018-0022-7
pii: S1933-0219(22)00392-0
pmc: PMC6202286
mid: NIHMS949312
doi:
Substances chimiques
Interleukin-17
0
Interleukin-4
207137-56-2
Interferon-gamma
82115-62-6
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
457-467Subventions
Organisme : NIDDK NIH HHS
ID : P01 DK094779
Pays : United States
Organisme : NIH HHS
ID : P40 OD010995
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK069434
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI094756
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK046763
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NIH HHS
ID : S10 OD016290
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Références
Integrative HMPRNC. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 16, 276–289 (2014).
doi: 10.1016/j.chom.2014.08.014
Huttenhower, C., Kostic, A. D. & Xavier, R. J. Inflammatory bowel disease as a model for translating the microbiome. Immunity 40, 843–854 (2014).
doi: 10.1016/j.immuni.2014.05.013
Sartor, R. B. & Wu, G. D. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology 152, 327–339.e324 (2017).
doi: 10.1053/j.gastro.2016.10.012
Brestoff, J. R. & Artis, D. Commensal bacteria at the interface of host metabolism and the immune system. Nat. Immunol. 14, 676–684 (2013).
doi: 10.1038/ni.2640
Dorrestein, P. C., Mazmanian, S. K. & Knight, R. Finding the missing links among metabolites, microbes, and the host. Immunity 40, 824–832 (2014).
doi: 10.1016/j.immuni.2014.05.015
Thorburn, A. N., Macia, L. & Mackay, C. R. Diet, metabolites, and “western-lifestyle” inflammatory diseases. Immunity 40, 833–842 (2014).
doi: 10.1016/j.immuni.2014.05.014
Kaiko, G. E. et al. The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 167, 1137 (2016).
doi: 10.1016/j.cell.2016.10.034
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
doi: 10.1038/nature12721
Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).
doi: 10.1016/j.chom.2014.02.005
Tong, M. et al. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. ISME J. 8, 2193–2206 (2014).
doi: 10.1038/ismej.2014.64
Lewis, J. D. et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 18, 489–500 (2015).
doi: 10.1016/j.chom.2015.09.008
Gao, Z. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509–1517 (2009).
doi: 10.2337/db08-1637
Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).
doi: 10.1126/science.1241165
Chang, P. V., Hao, L., Offermanns, S. & Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA 111, 2247–2252 (2014).
doi: 10.1073/pnas.1322269111
Mascanfroni, I. D. et al. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-alpha. Nat. Med. 21, 638–646 (2015).
doi: 10.1038/nm.3868
Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).
doi: 10.1126/science.1223490
Knights, D. et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med. 6, 107 (2014).
doi: 10.1186/s13073-014-0107-1
Khor, B., Gardet, A. & Xavier, R. J. Genetics and pathogenesis of inflammatory bowel disease. Nature 474, 307–317 (2011).
doi: 10.1038/nature10209
Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).
doi: 10.1038/nature11582
Yen, D. et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116, 1310–1316 (2006).
doi: 10.1172/JCI21404
Fujino, S. et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52, 65–70 (2003).
doi: 10.1136/gut.52.1.65
Kleinschek, M. A. et al. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J. Exp. Med. 206, 525–534 (2009).
doi: 10.1084/jem.20081712
Bogaert, S. et al. Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease. BMC Immunol. 11, 61 (2010).
doi: 10.1186/1471-2172-11-61
Kobayashi, T. et al. IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease. Gut 57, 1682–1689 (2008).
doi: 10.1136/gut.2007.135053
Neurath, M. F. New targets for mucosal healing and therapy in inflammatory bowel diseases. Mucosal Immunol. 7, 6–19 (2014).
doi: 10.1038/mi.2013.73
Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693–1700 (2012).
doi: 10.1136/gutjnl-2011-301668
Sandborn, W. J. et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N. Engl. J. Med. 367, 1519–1528 (2012).
doi: 10.1056/NEJMoa1203572
Sands, B. E. et al. OP025: a randomized, double-blind placebo-controlled phase 2a induction study of MEDI2070 (anti-p19 antibody) in patients with active Crohn’s disease who have failed anti-TNF antibody therapy. J. Crohn’s Colitis 9, S15–S16 (2015).
Targan, S. R. et al. Mo2083: a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of AMG 827 in subjects with moderate to severe Crohn’s disease. Gastroenterology 143, e26 (2012).
doi: 10.1053/j.gastro.2012.07.084
Colombel, J. F., Sendid, B., Jouault, T. & Poulain, D. Secukinumab failure in Crohn’s disease: the yeast connection? Gut 62, 800–801 (2013).
doi: 10.1136/gutjnl-2012-304154
Maxwell, J. R. et al. Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation. Immunity 43, 739–750 (2015).
doi: 10.1016/j.immuni.2015.08.019
Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13, R79 (2012).
doi: 10.1186/gb-2012-13-9-r79
Wilson, N. J. et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat. Immunol. 8, 950–957 (2007).
doi: 10.1038/ni1497
Wang, C. et al. CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity. Cell 163, 1413–1427 (2015).
doi: 10.1016/j.cell.2015.10.068
Pacheco, R. et al. Glutamate released by dendritic cells as a novel modulator of T cell activation. J. Immunol. 177, 6695–6704 (2006).
doi: 10.4049/jimmunol.177.10.6695
Wishart, D. S. et al. HMDB 3.0--The Human Metabolome Database in 2013. Nucleic Acids Res. 41, D801–D807 (2013).
doi: 10.1093/nar/gks1065
Yun, J. et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350, 1391–1396 (2015).
doi: 10.1126/science.aaa5004
Macintyre, A. N. et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 20, 61–72 (2014).
doi: 10.1016/j.cmet.2014.05.004
Buck, M. D., O’Sullivan, D. & Pearce, E. L. T cell metabolism drives immunity. J. Exp. Med. 212, 1345–1360 (2015).
doi: 10.1084/jem.20151159
Slack, M., Wang, T. & Wang, R. T cell metabolic reprogramming and plasticity. Mol. Immunol. 68, 507–512 (2015).
doi: 10.1016/j.molimm.2015.07.036
Hancock, R. D. & Viola, R. Biotechnological approaches for L-ascorbic acid production. Trends Biotechnol. 20, 299–305 (2002).
doi: 10.1016/S0167-7799(02)01991-1
DuPage, M. & Bluestone, J. A. Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease. Nat. Rev. Immunol. 16, 149–163 (2016).
doi: 10.1038/nri.2015.18
Sallusto, F. Heterogeneity of human CD4(+) T cells against microbes. Annu. Rev. Immunol. 34, 317–334 (2016).
doi: 10.1146/annurev-immunol-032414-112056
Hong, J. M., Kim, J. H., Kang, J. S., Lee, W. J. & Hwang, Y. I. Vitamin C is taken up by human T cells via sodium-dependent vitamin C transporter 2 (SVCT2) and exerts inhibitory effects on the activation of these cells in vitro. Anat. Cell Biol. 49, 88–98 (2016).
doi: 10.5115/acb.2016.49.2.88
Maratou, E. et al. Glucose transporter expression on the plasma membrane of resting and activated white blood cells. Eur. J. Clin. Invest. 37, 282–290 (2007).
doi: 10.1111/j.1365-2362.2007.01786.x
Rumsey, S. C. et al. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J. Biol. Chem. 272, 18982–18989 (1997).
doi: 10.1074/jbc.272.30.18982
Vera, J. C., Rivas, C. I., Fischbarg, J. & Golde, D. W. Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature 364, 79–82 (1993).
doi: 10.1038/364079a0
May, J. M., Mendiratta, S., Hill, K. E. & Burk, R. F. Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. J. Biol. Chem. 272, 22607–22610 (1997).
doi: 10.1074/jbc.272.36.22607
Winkler, B. S., Orselli, S. M. & Rex, T. S. The redox couple between glutathione and ascorbic acid: a chemical and physiological perspective. Free Radic. Biol. Med. 17, 333–349 (1994).
doi: 10.1016/0891-5849(94)90019-1
Hwang, N. R. et al. Oxidative modifications of glyceraldehyde-3-phosphate dehydrogenase play a key role in its multiple cellular functions. Biochem. J. 423, 253–264 (2009).
doi: 10.1042/BJ20090854
Shenton, D. & Grant, C. M. Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae. Biochem. J. 374, 513–519 (2003).
doi: 10.1042/bj20030414
Ravichandran, V., Seres, T., Moriguchi, T., Thomas, J. A. & Johnston, R. B. Jr. S-thiolation of glyceraldehyde-3-phosphate dehydrogenase induced by the phagocytosis-associated respiratory burst in blood monocytes. J. Biol. Chem. 269, 25010–25015 (1994).
pubmed: 7929187
Ullah, M. F., Khan, H. Y., Zubair, H., Shamim, U. & Hadi, S. M. The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother. Pharmacol. 67, 103–110 (2011).
doi: 10.1007/s00280-010-1290-4
Franchi, L. et al. Inhibiting oxidative phosphorylation in vivo restrains Th17 effector responses and ameliorates murine colitis. J. Immunol. 198, 2735–2746 (2017).
doi: 10.4049/jimmunol.1600810
Fiorani, M. et al. The mitochondrial transporter of ascorbic acid functions with high affinity in the presence of low millimolar concentrations of sodium and in the absence of calcium and magnesium. Biochim. Biophys. Acta 1848, 1393–1401 (2015).
doi: 10.1016/j.bbamem.2015.03.009
Tsukaguchi, H. et al. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature 399, 70–75 (1999).
doi: 10.1038/19986
Savini, I., Rossi, A., Pierro, C., Avigliano, L. & Catani, M. V. SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids 34, 347–355 (2008).
doi: 10.1007/s00726-007-0555-7
Li, X., Cobb, C. E. & May, J. M. Mitochondrial recycling of ascorbic acid from dehydroascorbic acid: dependence on the electron transport chain. Arch. Biochem. Biophys. 403, 103–110 (2002).
doi: 10.1016/S0003-9861(02)00205-9
Sasidharan Nair, V., Song, M. H. & Oh, K. I. Vitamin C facilitates demethylation of the Foxp3 enhancer in a Tet-dependent manner. J. Immunol. 196, 2119–2131 (2016).
doi: 10.4049/jimmunol.1502352
Yue, X. et al. Control of Foxp3 stability through modulation of TET activity. J. Exp. Med. 213, 377–397 (2016).
doi: 10.1084/jem.20151438
Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N. & Yagi, K. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 269, 13685–13688 (1994).
pubmed: 8175804
Naidu, K. A. Vitamin C in human health and disease is still a mystery? An overview. Nutr. J. 2, 7 (2003).
doi: 10.1186/1475-2891-2-7
Costa, K. C., Glasser, N. R., Conway, S. J. & Newman, D. K. Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms. Science 355, 170–173 (2017).
doi: 10.1126/science.aag3180
Vera, J. C. et al. Resolution of the facilitated transport of dehydroascorbic acid from its intracellular accumulation as ascorbic acid. J. Biol. Chem. 270, 23706–23712 (1995).
doi: 10.1074/jbc.270.40.23706
Amir Shaghaghi, M., Bernstein, C. N., Serrano Leon, A., El-Gabalawy, H. & Eck, P. Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn disease. Am. J. Clin. Nutr. 99, 378–383 (2014).
doi: 10.3945/ajcn.113.068015
Hengstermann, S. et al. Altered status of antioxidant vitamins and fatty acids in patients with inactive inflammatory bowel disease. Clin. Nutr. 27, 571–578 (2008).
doi: 10.1016/j.clnu.2008.01.007
Langille, M. G. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat. Biotechnol. 31, 814–821 (2013).
doi: 10.1038/nbt.2676
Abubucker, S. et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput. Biol. 8, e1002358 (2012).
doi: 10.1371/journal.pcbi.1002358
Sokol, P. A., Darling, P., Woods, D. E., Mahenthiralingam, E. & Kooi, C. Role of ornibactin biosynthesis in the virulence of Burkholderia cepacia: characterization of pvdA, the gene encoding L-ornithine N(5)-oxygenase. Infect. Immun. 67, 4443–4455 (1999).
pubmed: 10456885
pmcid: 96763
Mc, F. J. The nephelometer:aN instrument for estimating the number of bacteria in suspensions used for calculating the opsonic index and for vaccines. J. Am. Med. Assoc. XLIX, 1176–1178 (1907).
doi: 10.1001/jama.1907.25320140022001f