Priming dendritic cells for Th2 polarization: Lessons learned from helminths and implications for metabolic disorders

Frontiers in Immunology

Volumn 5, Issue OCT, 2014, Pages

  Hussaarts, Leonie ^a   Yazdanbakhsh, Maria ^a   Guigas, Bruno ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Antigen presenting cells; Dendritic cells; Helminth; Insulin resistance; Metabolic diseases; Obesity; Th2 cells; Type 2 inflammation

Indexed keywords

B7 ANTIGEN; CD40 ANTIGEN; CD86 ANTIGEN; CRYOPYRIN; CYTOKINE; GLYCOPROTEIN P 15095; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLAMMASOME; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 33; LECTIN RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; OX40 LIGAND; PARASITE ANTIGEN; PATTERN RECOGNITION RECEPTOR; PROTEIN BCL 3; STAT5 PROTEIN; T LYMPHOCYTE RECEPTOR; THYMIC STROMAL LYMPHOPOIETIN; TOLL LIKE RECEPTOR;

ANTIGEN PRESENTING CELL; CELL MATURATION; CELL PROLIFERATION; CELLULAR DISTRIBUTION; DENDRITIC CELL; DOWN REGULATION; HELMINTH; HELMINTHIASIS; HUMAN; IMMUNE RESPONSE; INSULIN SENSITIVITY; MEMBRANE POLARIZATION AND DEPOLARIZATION; METABOLIC DISORDER; NONHUMAN; PROTEIN EXPRESSION; SHORT SURVEY; SIGNAL TRANSDUCTION; TISSUE INJURY;

EID: 84918780025     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00499     Document Type: Short Survey

References (116)

1. Gause WC, Wynn TA, Allen JE. Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nat Rev Immunol (2013) 13(8):607-14. doi:10.1038/nri3476
2. Anthony RM, Rutitzky LI, Urban JF Jr, Stadecker MJ, Gause WC. Protective immune mechanisms in helminth infection. Nat Rev Immunol (2007) 7(12):975-87. doi:10.1038/nri2199
3. Chen F, Liu Z, Wu W, Rozo C, Bowdridge S, Millman A, et al. An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection. Nat Med (2012) 18(2):260-6. doi:10.1038/nm.2628
4. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol (2011) 12(11):1045-54. doi:10.1031/ni.2131
5. Herbert DR, Orekov T, Roloson A, Ilies M, Perkins C, O'Brien W, et al. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J Immunol (2010) 184(11):6438-46. doi:10.4049/jimmunol.0902009
6. Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM, et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog (2009) 5(4):e1000371. doi:10.1371/journal.ppat.1000371
7. Chawla A, Nguyen KD, Goh YP. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol (2011) 11(11):738-49. doi:10.1038/nri3071
8. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science (2011) 332(6026):243-7. doi:10.1126/science.1201475
9. Yang Z, Grinchuk V, Smith A, Qin B, Bohl JA, Sun R, et al. Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity. Infect Immun (2013) 81(6):1905-14. doi:10.1128/IAI.00053-13
10. Wiria AE, Sartono E, Supali T, Yazdanbakhsh M. Helminth infections, type-2 immune response, and metabolic syndrome. PLoS Pathog (2014) 10(7):e1004140. doi:10.1371/journal.ppat.1004140
11. Pulendran B, Tang H, Manicassamy S. Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat Immunol (2010) 11(8):647-55. doi:10.1038/ni.1894
12. Phythian-Adams AT, Cook PC, Lundie RJ, Jones LH, Smith KA, Barr TA, et al. CD11c depletion severely disrupts Th2 induction and development in vivo. J Exp Med (2010) 207(10):2089-96. doi:10.1084/jem.20100734
13. Smith KA, Harcus Y, Garbi N, Hammerling GJ, MacDonald AS, Maizels RM. Type 2 innate immunity in helminth infection is induced redundantly and acts autonomously following CD11c(+) cell depletion. Infect Immun (2012) 80(10):3481-9. doi:10.1128/IAI.00436-12
14. Smith KA, Hochweller K, Hammerling GJ, Boon L, MacDonald AS, Maizels RM. Chronic helminth infection promotes immune regulation in vivo through dominance of CD11cloC. J Immunol (2011) 186(12):7098-109. doi:10.4049/jimmunol.1003636
15. Briseno CG, Murphy TL, Murphy KM. Complementary diversification of dendritic cells and innate lymphoid cells. Curr Opin Immunol (2014) 29:69-78. doi:10.1016/j.coi.2014.04.006
16. Kumamoto Y, Linehan M, Weinstein JS, Laidlaw BJ, Craft JE, Iwasaki A. CD301b(+) dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity (2013) 39(4):733-43. doi:10.1016/j.immuni.2013.08.029
17. Gao Y, Nish SA, Jiang R, Hou L, Licona-Limon P, Weinstein JS, et al. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity (2013) 39(4):722-32. doi:10.1016/j.immuni.2013.08.028
18. Connor LM, Tang SC, Camberis M, Le GG, Ronchese F. Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J Immunol (2014) 193(6):2709-17. doi:10.4049/jimmunol.1400374
19. Leon B, Ballesteros-Tato A, Browning JL, Dunn R, Randall TD, Lund FE. Regulation of T(H)2 development by CXCR5+ dendritic cells and lymphotoxin-expressing B cells. Nat Immunol (2012) 13(7):681-90. doi:10.1038/ni.2309
20. Tang H, Cao W, Kasturi SP, Ravindran R, Nakaya HI, Kundu K, et al. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol (2010) 11(7):608-17. doi:10.1038/ni.1883
21. Halim TY, Steer CA, Matha L, Gold MJ, Martinez-Gonzalez I, McNagny KM, et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity (2014) 40(3):425-35. doi:10.1016/j.immuni.2014.01.011
22. Kapsenberg ML. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol (2003) 3(12):984-93. doi:10.1038/nri1246
23. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science (2010) 327(5963):291-5. doi:10.1126/science.1183021
24. Aksoy E, Zouain CS, Vanhoutte F, Fontaine J, Pavelka N, Thieblemont N, et al. Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in dendritic cells. J Biol Chem (2005) 280(1):277-83. doi:10.1074/jbc.M411223200
25. van der Kleij D, Latz E, Brouwers JF, Kruize YC, Schmitz M, Kurt-Jones EA, et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. J Biol Chem (2002) 277(50):48122-9. doi:10.1074/jbc.M206941200
26. Goodridge HS, Marshall FA, Else KJ, Houston KM, Egan C, Al-Riyami L, et al. Immunomodulation via novel use of TLR4 by the filarial nematode phosphorylcholine-containing secreted product, ES-62. J Immunol (2005) 174(1):284-93. doi:10.4049/jimmunol.174.1.284
27. Correale J, Farez M. Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol (2009) 183(9):5999-6012. doi:10.4049/jimmunol.0900897
28. Thomas PG, Carter MR, Atochina O, Da'Dara AA, Piskorska D, McGuire E, et al. Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like receptor 4-dependent mechanism. J Immunol (2003) 171(11):5837-41. doi:10.4049/jimmunol.171.11.5837
29. Kane CM, Jung E, Pearce EJ. Schistosoma mansoni egg antigen-mediated modulation of Toll-like receptor (TLR)-induced activation occurs independently of TLR2, TLR4, and MyD88. Infect Immun (2008) 76(12):5754-9. doi:10.1128/IAI.00497-08
30. Jankovic D, Kullberg MC, Caspar P, Sher A. Parasite-induced Th2 polarization is associated with down-regulated dendritic cell responsiveness to Th1 stimuli and a transient delay in T lymphocyte cycling. J Immunol (2004) 173(4):2419-27. doi:10.4049/jimmunol.173.4.2419
31. van LE, van Vliet SJ, Engering A, Garcia Vallejo JJ, Bank CM, Sanchez-Hernandez M, et al. Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation. Mol Immunol (2007) 44(10):2605-15. doi:10.1016/j.molimm.2006.12.012
32. Ritter M, Gross O, Kays S, Ruland J, Nimmerjahn F, Saijo S, et al. Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proc Natl Acad Sci U S A (2010) 107(47):20459-64. doi:10.1073/pnas.1010337107
33. van D I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, et al. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology (2003) 13(6):471-8. doi:10.1093/glycob/cwg052
34. Gringhuis SI, Kaptein TM, Wevers BA, Mesman AW, Geijtenbeek TB. Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKepsilon- and CYLD-dependent Bcl3 activation. Nat Commun (2014) 5:3898. doi:10.1038/ncomms4898
35. Terrazas CA, Alcantara-Hernandez M, Bonifaz L, Terrazas LI, Satoskar AR. Helminth-excreted/secreted products are recognized by multiple receptors on DCs to block the TLR response and bias Th2 polarization in a cRAF dependent pathway. FASEB J (2013) 27(11):4547-60. doi:10.1096/fj.13-228932
36. Terrazas CA, Gomez-Garcia L, Terrazas LI. Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: a critical role for carbohydrates but not for STAT6 signaling. Int J Parasitol (2010) 40(9):1051-62. doi:10.1016/j.ijpara.2010.02.016
37. Meevissen MH, Wuhrer M, Doenhoff MJ, Schramm G, Haas H, Deelder AM, et al. Structural characterization of glycans on omega-1, a major Schistosoma mansoni egg glycoprotein that drives Th2 responses. J Proteome Res (2010) 9(5):2630-42. doi:10.1021/pr100081c
38. Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, et al. Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med (2009) 206(8):1673-80. doi:10.1084/jem.20082460
39. Steinfelder S, Andersen JF, Cannons JL, Feng CG, Joshi M, Dwyer D, et al. The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1). J Exp Med (2009) 206(8):1681-90. doi:10.1084/jem.20082462
40. Everts B, Hussaarts L, Driessen NN, Meevissen MH, Schramm G, van der Ham AJ, et al. Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor. J Exp Med (2012) 209(10):1753-67. doi:10.1084/jem.20111381
41. Swamy M, Jamora C, Havran W, Hayday A. Epithelial decision makers: in search of the 'epimmunome'. Nat Immunol (2010) 11(8):656-65. doi:10.1038/ni.1905
42. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol (2002) 3(7):673-80. doi:10.1038/ni805
43. Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, Comeau MR, et al. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med (2009) 206(3):655-67. doi:10.1084/jem.20081499
44. Massacand JC, Stettler RC, Meier R, Humphreys NE, Grencis RK, Marsland BJ, et al. Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function. Proc Natl Acad Sci U S A (2009) 106(33):13968-73. doi:10.1073/pnas.0906367106
45. Ramalingam TR, Pesce JT, Mentink-Kane MM, Madala S, Cheever AW, Comeau MR, et al. Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin. J Immunol (2009) 182(10):6452-9. doi:10.4049/jimmunol.0900181
46. Giacomin PR, Siracusa MC, Walsh KP, Grencis RK, Kubo M, Comeau MR, et al. Thymic stromal lymphopoietin-dependent basophils promote Th2 cytokine responses following intestinal helminth infection. J Immunol (2012) 189(9):4371-8. doi:10.4049/jimmunol.1200691
47. Besnard AG, Togbe D, Guillou N, Erard F, Quesniaux V, Ryffel B. IL-33-activated dendritic cells are critical for allergic airway inflammation. Eur J Immunol (2011) 41(6):1675-86. doi:10.1002/eji.201041033
48. Eiwegger T, Akdis CA. IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma. Eur J Immunol (2011) 41(6):1535-8. doi:10.1002/eji.201141668
49. Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK. IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol (2008) 180(4):2443-9. doi:10.4049/jimmunol.180.4.2443
50. Townsend MJ, Fallon PG, Matthews DJ, Jolin HE, McKenzie AN. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses. J Exp Med (2000) 191(6):1069-76. doi:10.1084/jem.191.6.1069
51. Hung LY, Lewkowich IP, Dawson LA, Downey J, Yang Y, Smith DE, et al. IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms. Proc Natl Acad Sci U S A (2013) 110(1):282-7. doi:10.1073/pnas.1206587110
52. Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, et al. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med (2006) 203(4):1105-16. doi:10.1084/jem.20051615
53. Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med (2007) 204(8):1837-47. doi:10.1084/jem.20070406
54. Arthur JS, Ley SC. Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol (2013) 13(9):679-92. doi:10.1038/nri3495
55. Kane CM, Cervi L, Sun J, McKee AS, Masek KS, Shapira S, et al. Helminth antigens modulate TLR-initiated dendritic cell activation. J Immunol (2004) 173(12):7454-61. doi:10.4049/jimmunol.173.12.7454
56. Cervi L, MacDonald AS, Kane C, Dzierszinski F, Pearce EJ. Cutting edge: dendritic cells copulsed with microbial and helminth antigens undergo modified maturation, segregate the antigens to distinct intracellular compartments, and concurrently induce microbe-specific Th1 and helminth-specific Th2 responses. J Immunol (2004) 172(4):2016-20. doi:10.4049/jimmunol.172.4.2016
57. Rigano R, Buttari B, Profumo E, Ortona E, Delunardo F, Margutti P, et al. Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response. Infect Immun (2007) 75(4):1667-78. doi:10.1128/IAI.01156-06
58. Balic A, Harcus Y, Holland MJ, Maizels RM. Selective maturation of dendritic cells by Nippostrongylus brasiliensis-secreted proteins drives Th2 immune responses. Eur J Immunol (2004) 34(11):3047-59. doi:10.1002/eji.200425167
59. Segura M, Su Z, Piccirillo C, Stevenson MM. Impairment of dendritic cell function by excretory-secretory products: a potential mechanism for nematode-induced immunosuppression. Eur J Immunol (2007) 37(7):1887-904. doi:10.1002/eji.200636553
60. Brannstrom K, Sellin ME, Holmfeldt P, Brattsand M, Gullberg M. The Schistosoma mansoni protein Sm16/SmSLP/SmSPO-1 assembles into a nine-subunit oligomer with potential To inhibit Toll-like receptor signaling. Infect Immun (2009) 77(3):1144-54. doi:10.1128/IAI.01126-08
61. Everts B, Smits HH, Hokke CH, Yazdanbakhsh M. Helminths and dendritic cells: sensing and regulating via pattern recognition receptors, Th2 and Treg responses. Eur J Immunol (2010) 40(6):1525-37. doi:10.1002/eji.200940109
62. Agrawal S, Agrawal A, Doughty B, Gerwitz A, Blenis J, Van DT, et al. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol (2003) 171(10):4984-9. doi:10.4049/jimmunol.171.10.4984
63. Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu YJ. Distinct signal codes generate dendritic cell functional plasticity. Sci Signal (2010) 3(105):ra4. doi:10.1126/scisignal.2000567
64. Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med (2005) 202(9):1213-23. doi:10.1084/jem.20051135
65. Artis D, Kane CM, Fiore J, Zaph C, Shapira S, Joyce K, et al. Dendritic cell-intrinsic expression of NF-kappa B1 is required to promote optimal Th2 cell differentiation. J Immunol (2005) 174(11):7154-9. doi:10.4049/jimmunol.174.11.7154
66. Thomas PG, Carter MR, Da'Dara AA, DeSimone TM, Harn DA. A helminth glycan induces APC maturation via alternative NF-kappa B activation independent of I kappa B alpha degradation. J Immunol (2005) 175(4):2082-90. doi:10.4049/jimmunol.175.4.2082
67. Bell BD, Kitajima M, Larson RP, Stoklasek TA, Dang K, Sakamoto K, et al. The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses. Nat Immunol (2013) 14(4):364-71. doi:10.1038/ni.2541
68. Bufe A, Spangfort MD, Kahlert H, Schlaak M, Becker WM. The major birch pollen allergen, Bet v 1, shows ribonuclease activity. Planta (1996) 199(3):413-5. doi:10.1007/BF00195733
69. Kao R, Martinez-Ruiz A, Martinez del PA, Crameri R, Davies J. Mitogillin and related fungal ribotoxins. Methods Enzymol (2001) 341:324-35. doi:10.1016/S0076-6879(01)41161-X
70. Yang D, Chen Q, Su SB, Zhang P, Kurosaka K, Caspi RR, et al. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. J Exp Med (2008) 205(1):79-90. doi:10.1084/jem.20062027
71. Hartmann S, Lucius R. Modulation of host immune responses by nematode cystatins. Int J Parasitol (2003) 33(11):1291-302. doi:10.1016/S0020-7519(03)00163-2
72. Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity (2013) 38(4):633-43. doi:10.1016/j.immuni.2013.04.005
73. Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood (2010) 115(23):4742-9. doi:10.1182/blood-2009-10-249540
74. Everts B, Amiel E, Huang SC, Smith AM, Chang CH, Lam WY, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKvarepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol (2014) 15(4):323-32. doi:10.1038/ni.2833
75. Amiel E, Everts B, Freitas TC, King IL, Curtis JD, Pearce EL, et al. Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J Immunol (2012) 189(5):2151-8. doi:10.4049/jimmunol.1103741
76. Amiel E, Everts B, Fritz D, Beauchamp S, Ge B, Pearce EL, et al. Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic cells by preserving mitochondrial function. J Immunol (2014) 193(6):2821-30. doi:10.4049/jimmunol.1302498
77. Hussaarts L, Smits HH, Schramm G, van der Ham AJ, van der Zon GC, Haas H, et al. Rapamycin and omega-1: mTOR-dependent and -independent Th2 skewing by human dendritic cells. Immunol Cell Biol (2013) 91(7):486-9. doi:10.1038/icb.2013.31
78. Dong C, Flavell RA. Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res (2000) 2(3):179-88. doi:10.1186/ar85
79. Jankovic D, Steinfelder S, Kullberg MC, Sher A. Mechanisms underlying helminth-induced Th2 polarization: default, negative or positive pathways? Chem Immunol Allergy (2006) 90:65-81. doi:10.1159/000088881
80. Oswald IP, Caspar P, Jankovic D, Wynn TA, Pearce EJ, Sher A. IL-12 inhibits Th2 cytokine responses induced by eggs of Schistosoma mansoni. J Immunol (1994) 153(4):1707-13.
81. Jankovic D, Kullberg MC, Hieny S, Caspar P, Collazo CM, Sher A. In the absence of IL-12, CD4(+) T cell responses to intracellular pathogens fail to default to a Th2 pattern and are host protective in an IL-10(-/-) setting. Immunity (2002) 16(3):429-39. doi:10.1016/S1074-7613(02)00278-9
82. Cook PC, Jones LH, Jenkins SJ, Wynn TA, Allen JE, MacDonald AS. Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo. Proc Natl Acad Sci U S A (2012) 109(25):9977-82. doi:10.1073/pnas.1121231109
83. de Jong EC, Vieira PL, Kalinski P, Schuitemaker JH, Tanaka Y, Wierenga EA, et al. Microbial compounds selectively induce Th1 cell-promoting or Th2 cell-promoting dendritic cells in vitro with diverse th cell-polarizing signals. J Immunol (2002) 168(4):1704-9. doi:10.4049/jimmunol.168.4.1704
84. Amsen D, Blander JM, Lee GR, Tanigaki K, Honjo T, Flavell RA. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell (2004) 117(4):515-26. doi:10.1016/S0092-8674(04)00451-9
85. Krawczyk CM, Sun J, Pearce EJ. Th2 differentiation is unaffected by Jagged2 expression on dendritic cells. J Immunol (2008) 180(12):7931-7. doi:10.4049/jimmunol.180.12.7931
86. Worsley AG, LeibundGut-Landmann S, Slack E, Phng LK, Gerhardt H, Reis e Sousa C, et al. Dendritic cell expression of the Notch ligand jagged2 is not essential for Th2 response induction in vivo. Eur J Immunol (2008) 38(4):1043-9. doi:10.1002/eji.200737335
87. van RE, Everts B, Retra K, Phylipsen M, van Hellemond JJ, Tielens AG, et al. Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization. BMC Immunol (2009) 10:9. doi:10.1186/1471-2172-10-9
88. MacDonald AS, Straw AD, Dalton NM, Pearce EJ. Cutting edge: Th2 response induction by dendritic cells: a role for CD40. J Immunol (2002) 168(2):537-40. doi:10.4049/jimmunol.168.2.537
89. MacDonald AS, Patton EA, La Flamme AC, Araujo MI, Huxtable CR, Bauman B, et al. Impaired Th2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction. J Immunol (2002) 168(9):4643-9. doi:10.4049/jimmunol.168.9.4643
90. Jenkins SJ, Perona-Wright G, Worsley AG, Ishii N, MacDonald AS. Dendritic cell expression of OX40 ligand acts as a costimulatory, not polarizing, signal for optimal Th2 priming and memory induction in vivo. J Immunol (2007) 179(6):3515-23. doi:10.4049/jimmunol.179.6.3515
91. Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K. Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J Exp Med (1995) 182(5):1591-6. doi:10.1084/jem.182.5.1591
92. Hosken NA, Shibuya K, Heath AW, Murphy KM, O'Garra A. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med (1995) 182(5):1579-84. doi:10.1084/jem.182.5.1579
93. Boonstra A, Asselin-Paturel C, Gilliet M, Crain C, Trinchieri G, Liu YJ, et al. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J Exp Med (2003) 197(1):101-9. doi:10.1084/jem.20021908
94. van PN, Klauschen F, Germain RNT-. Cell-Receptor-Dependent Signal Intensity Dominantly Controls CD4(+) T Cell Polarization In vivo. Immunity (2014) 41(1):63-74. doi:10.1016/j.immuni.2014.06.003
95. Pulendran B, Artis D. New paradigms in type 2 immunity. Science (2012) 337(6093):431-5. doi:10.1126/science.1221064
96. Ricardo-Gonzalez RR, Red EA, Odegaard JI, Jouihan H, Morel CR, Heredia JE, et al. IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity. Proc Natl Acad Sci U S A (2010) 107(52):22617-22. doi:10.1073/pnas.1009152108
97. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol (2011) 11(2):98-107. doi:10.1038/nri2925
98. Bhargava P, Li C, Stanya KJ, Jacobi D, Dai L, Liu S, et al. Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways. Nat Med (2012) 18(11):1665-72. doi:10.1038/nm.2962
99. Doenhoff MJ, Stanley RG, Griffiths K, Jackson CL. An anti-atherogenic effect of Schistosoma mansoni infections in mice associated with a parasite-induced lowering of blood total cholesterol. Parasitology (2002) 125(Pt 5):415-21. doi:10.1017/S0031182002002275
100. Wolfs IM, Stoger JL, Goossens P, Pottgens C, Gijbels MJ, Wijnands E, et al. Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis. FASEB J (2014) 28(1):288-99. doi:10.1096/fj.13-235911
101. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med (2009) 15(8):921-9. doi:10.1038/nm.2001
102. Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med (2013) 210(3):535-49. doi:10.1084/jem.20121964
103. Hams E, Locksley RM, McKenzie AN, Fallon PG. Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice. J Immunol (2013) 191(11):5349-53. doi:10.4049/jimmunol.1301176
104. Aravindhan V, Mohan V, Surendar J, Muralidhara RM, Pavankumar N, Deepa M, et al. Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83). PLoS Negl Trop Dis (2010) 4(6):e707. doi:10.1371/journal.pntd.0000707
105. Chen Y, Lu J, Huang Y, Wang T, Xu Y, Xu M, et al. Association of previous schistosome infection with diabetes and metabolic syndrome: a cross-sectional study in rural China. J Clin Endocrinol Metab (2013) 98(2):E283-7. doi:10.1210/jc.2012-2517
106. Steinman RM. Dendritic cells in vivo: a key target for a new vaccine science. Immunity (2008) 29(3):319-24. doi:10.1016/j.immuni.2008.08.001
107. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer (2012) 12(4):265-77. doi:10.1038/nrc3258
108. Thomson AW, Robbins PD. Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann Rheum Dis (2008) 67(Suppl 3):iii90-6. doi:10.1136/ard.2008.099176
109. Stefanovic-Racic M, Yang X, Turner MS, Mantell BS, Stolz DB, Sumpter TL, et al. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes (2012) 61(9):2330-9. doi:10.2337/db11-1523
110. Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes (2012) 61(9):2238-47. doi:10.2337/db11-1274
111. Moraes-Vieira PM, Yore MM, Dwyer PM, Syed I, Aryal P, Kahn BB. RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell Metab (2014) 19(3):512-26. doi:10.1016/j.cmet.2014.01.018
112. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, et al. Differential antigen processing by dendritic cell subsets in vivo. Science (2007) 315(5808):107-11. doi:10.1126/science.1136080
113. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med (2002) 196(12):1627-38. doi:10.1084/jem.20021598
114. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med (2004) 199(6):815-24. doi:10.1084/jem.20032220
115. Qin H, Wilson CA, Lee SJ, Zhao X, Benveniste EN. LPS induces CD40 gene expression through the activation of NF-kappaB and STAT-1alpha in macrophages and microglia. Blood (2005) 106(9):3114-22. doi:10.1182/blood-2005-02-0759
116. Goh F, Irvine KM, Lovelace E, Donnelly S, Jones MK, Brion K, et al. Selective induction of the Notch ligand Jagged-1 in macrophages by soluble egg antigen from Schistosoma mansoni involves ERK signalling. Immunology (2009) 127(3):326-37. doi:10.1111/j.1365-2567.2008.02979.x