The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity by Regulating Gut Microbiota Homeostasis

Cell Host and Microbe

Volumn 24, Issue 3, 2018, Pages 364-378.e6

  Truax, Agnieszka D ^a,b   Chen, Liang ^b   Tam, Jason W ^a   Cheng, Ning ^a   Guo, Hao ^a   Koblansky, A Alicia ^a,b   Chou, Wei Chun ^a,b   Wilson, Justin E ^a,b   Brickey, W June ^a,b   Petrucelli, Alex ^a,b   Liu, Rongrong ^a   Cooper, Daniel E ^e   Koenigsknecht, Mark J ^c   Young, Vincent B ^c   Netea, Mihai G ^d   Stienstra, Rinke ^d   Sartor, R Balfour ^b   Montgomery, Stephanie A ^a,b   Coleman, Rosalind A ^e   Ting, Jenny P Y ^a,b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e University of North Carolina   (United States)

Author keywords

Erysipelotrichaceae; inflammasome; inflammation; innate immunity; Lachnospiraceae; microbiota; NLRP12; obesity; short chain fatty acid; type 2 diabetes

Indexed keywords

GLUCOSE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLAMMASOME; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; NLRP12 PROTEIN; NUCLEOTIDE BINDING OLIGOMERIZATION DOMAIN LIKE RECEPTOR; SHORT CHAIN FATTY ACID; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; NLRP12 PROTEIN, MOUSE; SIGNAL PEPTIDE;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC THERAPY; ARTICLE; BODY FAT; BODY MASS; BODY WEIGHT GAIN; COMPARATIVE STUDY; CONTROLLED STUDY; DIET INDUCED OBESITY; DYSBIOSIS; ENERGY EXPENDITURE; ENTERITIS; ENZYME ACTIVATION; ERYSIPELOTRICHACEAE; FEMALE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; HOMEOSTASIS; HUMAN; INGUINAL WHITE ADIPOSE TISSUE; INNATE IMMUNITY; INSULIN SIGNALING; INSULIN TOLERANCE TEST; INTESTINE FLORA; LACHNOSPIRACEAE; LIPID DIET; LOW FAT DIET; LUNG GAS EXCHANGE; MACROPHAGE; MALE; MAPK SIGNALING; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; RNA SEQUENCE; WAIST HIP RATIO; WHITE ADIPOSE TISSUE; ADULT; AGED; ANIMAL; BACTERIUM; C57BL MOUSE; CLASSIFICATION; GENETICS; IMMUNOLOGY; ISOLATION AND PURIFICATION; KNOCKOUT MOUSE; METABOLISM; MICROBIOLOGY; MIDDLE AGED; OBESITY;

ADIPOSE TISSUE; ADULT; AGED; ANIMALS; BACTERIA; FEMALE; GASTROINTESTINAL MICROBIOME; HOMEOSTASIS; HUMANS; IMMUNITY, INNATE; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MIDDLE AGED; OBESITY;

EID: 85052735485     PISSN: 19313128     EISSN: 19346069     Source Type: Journal    
DOI: 10.1016/j.chom.2018.08.009     Document Type: Article

References (70)

1. Allen, I.C., Lich, J.D., Arthur, J.C., Jania, C.M., Roberts, R.A., Callaway, J.B., Tilley, S.L., Ting, J.P., Characterization of NLRP12 during the development of allergic airway disease in mice. PLoS One, 7, 2012, e30612.
2. Allen, I.C., Wilson, J.E., Schneider, M., Lich, J.D., Roberts, R.A., Arthur, J.C., Woodford, R.M., Davis, B.K., Uronis, J.M., Herfarth, H.H., et al. NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-κB signaling. Immunity 36 (2012), 742–754.
3. Amano, S.U., Cohen, J.L., Vangala, P., Tencerova, M., Nicoloro, S.M., Yawe, J.C., Shen, Y., Czech, M.P., Aouadi, M., Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab. 19 (2014), 162–171.
4. Arthur, J.C., Lich, J.D., Ye, Z., Allen, I.C., Gris, D., Wilson, J.E., Schneider, M., Roney, K.E., O'Connor, B.P., Moore, C.B., et al. Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity. J. Immunol. 185 (2010), 4515–4519.
5. Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500 (2013), 232–236.
6. Bäckhed, F., Ding, H., Wang, T., Hooper, L.V., Koh, G.Y., Nagy, A., Semenkovich, C.F., Gordon, J.I., The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101 (2004), 15718–15723.
7. Ballak, D.B., van Diepen, J.A., Moschen, A.R., Jansen, H.J., Hijmans, A., Groenhof, G.J., Leenders, F., Bufler, P., Boekschoten, M.V., Müller, M., et al. IL-37 protects against obesity-induced inflammation and insulin resistance. Nat. Commun., 5, 2014, 4711.
8. Bouter, K.E., van Raalte, D.H., Groen, A.K., Nieuwdorp, M., Role of the gut microbiome in the pathogenesis of obesity and obesity-related metabolic dysfunction. Gastroenterology 152 (2017), 1671–1678.
9. Chassaing, B., Ley, R.E., Gewirtz, A.T., Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology 147 (2014), 1363–1377.e17.
10. Chen, G.Y., Shaw, M.H., Redondo, G., Núñez, G., The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res. 68 (2008), 10060–10067.
11. Chen, W., Liu, F., Ling, Z., Tong, X., Xiang, C., Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One, 7, 2012, e39743.
12. Chen, L., Wilson, J.E., Koenigsknecht, M.J., Chou, W.C., Montgomery, S.A., Truax, A.D., Brickey, W.J., Packey, C.D., Maharshak, N., Matsushima, G.K., et al. NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat. Immunol. 18 (2017), 541–551.
13. Cho, K.W., Morris, D.L., Lumeng, C.N., Flow cytometry analyses of adipose tissue macrophages. Methods Enzymol. 537 (2014), 297–314.
14. Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A.S., Obin, M.S., Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46 (2005), 2347–2355.
15. den Besten, G., van Eunen, K., Groen, A.K., Venema, K., Reijngoud, D.J., Bakker, B.M., The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54 (2013), 2325–2340.
16. Deshmane, S.L., Kremlev, S., Amini, S., Sawaya, B.E., Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon Cytokine Res. 29 (2009), 313–326.
17. Dey, N., Soergel, D.A., Repo, S., Brenner, S.E., Association of gut microbiota with post-operative clinical course in Crohn's disease. BMC Gastroenterol., 13, 2013, 131.
18. Dinh, D.M., Volpe, G.E., Duffalo, C., Bhalchandra, S., Tai, A.K., Kane, A.V., Wanke, C.A., Ward, H.D., Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J. Infect. Dis. 211 (2015), 19–27.
19. Divoux, A., Tordjman, J., Lacasa, D., Veyrie, N., Hugol, D., Aissat, A., Basdevant, A., Guerre-Millo, M., Poitou, C., Zucker, J.D., et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 59 (2010), 2817–2825.
20. Eckburg, P.B., Bik, E.M., Bernstein, C.N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S.R., Nelson, K.E., Relman, D.A., Diversity of the human intestinal microbial flora. Science 308 (2005), 1635–1638.
21. Fan, R., Toubal, A., Goñi, S., Drareni, K., Huang, Z., Alzaid, F., Ballaire, R., Ancel, P., Liang, N., Damdimopoulos, A., et al. Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes. Nat. Med. 22 (2016), 780–791.
22. Flegal, K.M., Carroll, M.D., Kit, B.K., Ogden, C.L., Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 307 (2012), 491–497.
23. Fleissner, C.K., Huebel, N., Abd El-Bary, M.M., Loh, G., Klaus, S., Blaut, M., Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br. J. Nutr. 104 (2010), 919–929.
24. Gevers, D., Kugathasan, S., Denson, L.A., Vázquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S.J., Yassour, M., et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15 (2014), 382–392.
25. Gharagozloo, M., Mahvelati, T.M., Imbeault, E., Gris, P., Zerif, E., Bobbala, D., Ilangumaran, S., Amrani, A., Gris, D., The nod-like receptor, Nlrp12, plays an anti-inflammatory role in experimental autoimmune encephalomyelitis. J. Neuroinflammation, 12, 2015, 198.
26. Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W.Z., Strowig, T., Thaiss, C.A., Kau, A.L., Eisenbarth, S.C., Jurczak, M.J., et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482 (2012), 179–185.
27. Hensrud, D.D., Klein, S., Extreme obesity: a new medical crisis in the United States. Mayo Clin. Proc. 81:10, Suppl (2006), S5–S10.
28. Hotamisligil, G.S., Arner, P., Caro, J.F., Atkinson, R.L., Spiegelman, B.M., Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Invest. 95 (1995), 2409–2415.
29. Khan, T., Muise, E.S., Iyengar, P., Wang, Z.V., Chandalia, M., Abate, N., Zhang, B.B., Bonaldo, P., Chua, S., Scherer, P.E., Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29 (2009), 1575–1591.
30. Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.M., Kennedy, S., et al., MetaHIT consortium. Richness of human gut microbiome correlates with metabolic markers. Nature 500 (2013), 541–546.
31. Ley, R.E., Bäckhed, F., Turnbaugh, P., Lozupone, C.A., Knight, R.D., Gordon, J.I., Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102 (2005), 11070–11075.
32. Ley, R.E., Turnbaugh, P.J., Klein, S., Gordon, J.I., Microbial ecology: human gut microbes associated with obesity. Nature 444 (2006), 1022–1023.
33. Li, G., Domenico, J., Jia, Y., Lucas, J.J., Gelfand, E.W., NF-kappaB-dependent induction of cathelicidin-related antimicrobial peptide in murine mast cells by lipopolysaccharide. Int. Arch. Allergy Immunol. 150 (2009), 122–132.
34. Lin, H.V., Frassetto, A., Kowalik, E.J. Jr., Nawrocki, A.R., Lu, M.M., Kosinski, J.R., Hubert, J.A., Szeto, D., Yao, X., Forrest, G., Marsh, D.J., Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One, 7, 2012, e35240.
35. Lukens, J.R., Gurung, P., Shaw, P.J., Barr, M.J., Zaki, M.H., Brown, S.A., Vogel, P., Chi, H., Kanneganti, T.D., The NLRP12 sensor negatively regulates autoinflammatory disease by modulating interleukin-4 production in T cells. Immunity 42 (2015), 654–664.
36. Lumeng, C.N., Bodzin, J.L., Saltiel, A.R., Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117 (2007), 175–184.
37. Martinez, F.O., Gordon, S., The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep., 6, 2014, 13.
38. Murano, I., Barbatelli, G., Parisani, V., Latini, C., Muzzonigro, G., Castellucci, M., Cinti, S., Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J. Lipid Res. 49 (2008), 1562–1568.
39. Nguyen, M.T., Favelyukis, S., Nguyen, A.K., Reichart, D., Scott, P.A., Jenn, A., Liu-Bryan, R., Glass, C.K., Neels, J.G., Olefsky, J.M., A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J. Biol. Chem. 282 (2007), 35279–35292.
40. Novakovic, B., Habibi, E., Wang, S.Y., Arts, R.J.W., Davar, R., Megchelenbrink, W., Kim, B., Kuznetsova, T., Kox, M., Zwaag, J., et al. β-glucan reverses the epigenetic state of LPS-induced immunological tolerance. Cell 167 (2016), 1354–1368.e14.
41. Ohshima, S., Saeki, Y., Mima, T., Sasai, M., Nishioka, K., Nomura, S., Kopf, M., Katada, Y., Tanaka, T., Suemura, M., Kishimoto, T., Interleukin 6 plays a key role in the development of antigen-induced arthritis. Proc. Natl. Acad. Sci. USA 95 (1998), 8222–8226.
42. Olefsky, J.M., Glass, C.K., Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72 (2010), 219–246.
43. Orr, J.S., Kennedy, A.J., Hasty, A.H., Isolation of adipose tissue immune cells. J. Vis. Exp.(75), 2013, e50707.
44. Ouchi, N., Parker, J.L., Lugus, J.J., Walsh, K., Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11 (2011), 85–97.
45. Park, H.S., Park, J.Y., Yu, R., Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res. Clin. Pract. 69 (2005), 29–35.
46. Park, E.J., Lee, J.H., Yu, G.Y., He, G., Ali, S.R., Holzer, R.G., Osterreicher, C.H., Takahashi, H., Karin, M., Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140 (2010), 197–208.
47. Park, S.H., Kang, K., Giannopoulou, E., Qiao, Y., Kang, K., Kim, G., Park-Min, K.H., Ivashkiv, L.B., Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation. Nat. Immunol. 18 (2017), 1104–1116.
48. Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., Geurts, L., Chilloux, J., Ottman, N., Duparc, T., Lichtenstein, L., et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23 (2017), 107–113.
49. Reichardt, N., Duncan, S.H., Young, P., Belenguer, A., McWilliam Leitch, C., Scott, K.P., Flint, H.J., Louis, P., Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 8 (2014), 1323–1335.
50. Ridaura, V.K., Faith, J.J., Rey, F.E., Cheng, J., Duncan, A.E., Kau, A.L., Griffin, N.W., Lombard, V., Henrissat, B., Bain, J.R., et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341, 2013, 1241214.
51. Sartor, R.B., Wu, G.D., Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology 152 (2017), 327–339.e4.
52. Shoelson, S.E., Lee, J., Yuan, M., Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int. J. Obes. Relat. Metab. Disord. 27:Suppl 3 (2003), S49–S52.
53. Smith, P.M., Howitt, M.R., Panikov, N., Michaud, M., Gallini, C.A., Bohlooly-Y, M., Glickman, J.N., Garrett, W.S., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341 (2013), 569–573.
54. Stienstra, R., Joosten, L.A., Koenen, T., van Tits, B., van Diepen, J.A., van den Berg, S.A., Rensen, P.C., Voshol, P.J., Fantuzzi, G., Hijmans, A., et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 12 (2010), 593–605.
55. Stienstra, R., van Diepen, J.A., Tack, C.J., Zaki, M.H., van de Veerdonk, F.L., Perera, D., Neale, G.A., Hooiveld, G.J., Hijmans, A., Vroegrijk, I., et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc. Natl. Acad. Sci. USA 108 (2011), 15324–15329.
56. Su, A.I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K.A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl. Acad. Sci. USA 101 (2004), 6062–6067.
57. Tzanavari, T., Giannogonas, P., Karalis, K.P., TNF-alpha and obesity. Curr. Dir. Autoimmun. 11 (2010), 145–156.
58. Vaishnava, S., Yamamoto, M., Severson, K.M., Ruhn, K.A., Yu, X., Koren, O., Ley, R., Wakeland, E.K., Hooper, L.V., The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 334 (2011), 255–258.
59. Vandanmagsar, B., Youm, Y.H., Ravussin, A., Galgani, J.E., Stadler, K., Mynatt, R.L., Ravussin, E., Stephens, J.M., Dixit, V.D., The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17 (2011), 179–188.
60. Vijay-Kumar, M., Aitken, J.D., Carvalho, F.A., Cullender, T.C., Mwangi, S., Srinivasan, S., Sitaraman, S.V., Knight, R., Ley, R.E., Gewirtz, A.T., Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328 (2010), 228–231.
61. Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., Ferrante, A.W. Jr., Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112 (2003), 1796–1808.
62. Wen, H., Gris, D., Lei, Y., Jha, S., Zhang, L., Huang, M.T., Brickey, W.J., Ting, J.P., Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12 (2011), 408–415.
63. Wu, F., Chakravarti, S., Differential expression of inflammatory and fibrogenic genes and their regulation by NF-kappaB inhibition in a mouse model of chronic colitis. J. Immunol. 179 (2007), 6988–7000.
64. Wu, C., Jin, X., Tsueng, G., Afrasiabi, C., Su, A.I., BioGPS: building your own mash-up of gene annotations and expression profiles. Nucleic Acids Res. 44:D1 (2016), D313–D316.
65. Xu, H., Barnes, G.T., Yang, Q., Tan, G., Yang, D., Chou, C.J., Sole, J., Nichols, A., Ross, J.S., Tartaglia, L.A., Chen, H., Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112 (2003), 1821–1830.
66. Xu, X., Grijalva, A., Skowronski, A., van Eijk, M., Serlie, M.J., Ferrante, A.W. Jr., Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab. 18 (2013), 816–830.
67. Yoshimura, T., McLean, M.H., Dzutsev, A.K., Yao, X., Chen, K., Huang, J., Gong, W., Zhou, J., Xiang, Y., H Badger, J., et al. The antimicrobial peptide CRAMP is essential for Colon homeostasis by maintaining microbiota balance. J. Immunol. 200 (2018), 2174–2185.
68. Yudkin, J.S., Stehouwer, C.D., Emeis, J.J., Coppack, S.W., C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?. Arterioscler. Thromb. Vasc. Biol. 19 (1999), 972–978.
69. Zaki, M.H., Vogel, P., Malireddi, R.K., Body-Malapel, M., Anand, P.K., Bertin, J., Green, D.R., Lamkanfi, M., Kanneganti, T.D., The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. Cancer Cell 20 (2011), 649–660.
70. Zhang, W., Hartmann, R., Tun, H.M., Elson, C.O., Khafipour, E., Garvey, W.T., Deletion of the Toll-like receptor 5 gene per se does not determine the gut microbiome profile that induces metabolic syndrome: environment trumps genotype. PLoS One, 11, 2016, e0150943.