Retinoic acid signalling in gastrointestinal parasite infections: Lessons from mouse models

Parasite Immunology

Volumn 34, Issue 7, 2012, Pages 351-359

  Hurst, R J M ^a   Else, K J ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Gastrointestinal; Helminth; Retinoic acid; Vitamin A

Indexed keywords

RETINOIC ACID; RETINOIC ACID RECEPTOR;

CD4+ T LYMPHOCYTE; DENDRITIC CELL; ENTERITIS; HELMINTHIASIS; HELPER CELL; HUMAN; IMMUNE RESPONSE; INTESTINE INFECTION; INTESTINE PARASITE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR BINDING; REGULATORY T LYMPHOCYTE; RETINOL DEFICIENCY; REVIEW; SIGNAL TRANSDUCTION; VITAMIN METABOLISM; VITAMIN SUPPLEMENTATION;

ANIMALS; DISEASE MODELS, ANIMAL; HELMINTHIASIS; INTESTINAL DISEASES; MICE; NEMATODE INFECTIONS; SIGNAL TRANSDUCTION; TRETINOIN;

EID: 84862026017     PISSN: 01419838     EISSN: 13653024     Source Type: Journal    
DOI: 10.1111/j.1365-3024.2012.01364.x     Document Type: Review

References (78)

1. D'Souza RM & D'Souza R. Vitamin A for the treatment of children with measles--a systematic review. J Trop Pediatr 2002; 48: 323-327.
2. Sommer A & Davidson FR. Assessment and control of vitamin A deficiency: the Annecy Accords. J Nutr 2002; 132: 2845S-2850S.
3. World Health Organization (1995) Assessment and control of vitamin A deficiency: the Annecy Accords. The Global Prevalence of Vitamin A Deficiency. Micronutrient Deficiency Information System (MDIS) Working Paper 2: WHO/NUT/95 3 World Health OrganizationGeneva, Switzerland. Available at: (Accessed 27 April 2012).
4. Imdad A, Yakoob MY, Sudfeld C, Haider BA, Black RE & Bhutta ZA. Impact of vitamin A supplementation on infant and childhood mortality. BMC Public Health 2011; 11(Suppl. 3): S20.
5. Hesham MS, Edariah AB & Norhayati M. Intestinal parasitic infections and micronutrient deficiency: a review. Med J Malaysia 2004; 59: 284-293.
6. Long KZ, Estrada-Garcia T, Rosado JL, et al. The effect of vitamin A supplementation on the intestinal immune response in Mexican children is modified by pathogen infections and diarrhea. J Nutr 2006; 136: 1365-1370.
7. LG Payne, KG Koski, E Ortega-Barria & ME Scott. Benefit of vitamin A supplementation on ascaris reinfection is less evident in stunted children. J Nutr 2007; 137: 1455-1459.
8. Aukrust P, Muller F, Ueland T, Svardal AM, Berge RK & Froland SS. Decreased vitamin A levels in common variable immunodeficiency: vitamin A supplementation in vivo enhances immunoglobulin production and downregulates inflammatory responses. Eur J Clin Invest 2000; 30: 252-259.
9. Chen Q & Ross AC. Retinoic acid promotes mouse splenic B cell surface IgG expression and maturation stimulated by CD40 and IL-4. Cell Immunol 2007; 249: 37-45.
10. Hoag KA, Nashold FE, Goverman J & Hayes CE. Retinoic acid enhances the T helper 2 cell development that is essential for robust antibody responses through its action on antigen-presenting cells. J Nutr 2002; 132: 3736-3739.
11. Iwata M, Eshima Y & Kagechika H. Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors. Int Immunol 2003; 15: 1017-1025.
12. Dawson HD, Collins G, Pyle R, et al. Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. BMC Immunol 2006; 7: 27.
13. Lovett-Racke AE & Racke MK. Retinoic acid promotes the development of Th2-like human myelin basic protein-reactive T cells. Cell Immunol 2002; 215: 54-60.
14. Benson MJ, Pino-Lagos K, Rosemblatt M & Noelle RJ. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 2007; 204: 1765-1774.
15. Blomhoff R & Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol 2006; 66: 606-630.
16. Mora JR, Iwata M & von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev 2008; 8: 685-698.
17. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007; 204: 1757-1764.
18. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C & Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity 2004; 21: 527-538.
19. Heyman RA, Mangelsdorf DJ, Dyck JA, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992; 68: 397-406.
20. de Lera AR, Bourguet W, Altucci L & Gronemeyer H. Design of selective nuclear receptor modulators: RAR and RXR as a case study. Nat Rev Drug Discov 2007; 6: 811-820.
21. Laffont S, Siddiqui KR & Powrie F. Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells. Eur J Immunol 2010; 40: 1877-1883.
22. Yokota A, Takeuchi H, Maeda N, et al. GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity. Int Immunol 2009; 21: 361-377.
23. Altucci L, Leibowitz MD, Ogilvie KM, de Lera AR & Gronemeyer H. RAR and RXR modulation in cancer and metabolic disease. Nat Rev Drug Discov 2007; 6: 793-810.
24. Clarke N, Germain P, Altucci L & Gronemeyer H. Retinoids: potential in cancer prevention and therapy. Expert Rev Mol Med 2004; 6: 1-23.
25. Kagechika H & Shudo K. Synthetic retinoids: recent developments concerning structure and clinical utility. J Med Chem 2005; 48: 5875-5883.
26. Mangelsdorf DJ, Borgmeyer U, Heyman RA, et al. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 1992; 6: 329-344.
27. Glass CK & Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000; 14: 121-141.
28. Smith SM, Levy NS & Hayes CE. Impaired immunity in vitamin A-deficient mice. J Nutr 1987; 117: 857-865.
29. Wilson JG, Roth CB & Warkany J. An analysis of the syndrome of malformations induced by maternal vitamin A deficiency Effects of restoration of vitamin A at various times during gestation. Am J Anat 1953; 92: 189-217.
30. Mark M, Ghyselinck NB & Chambon P. Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol 2006; 46: 451-480.
31. Kastner P, Mark M & Chambon P. Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life? Cell 1995; 83: 859-869.
32. Lefebvre P, Benomar Y & Staels B. Retinoid X receptors: common heterodimerization partners with distinct functions. Trends Endocrinol Metab 2010; 21: 676-683.
33. Cross M, Mangelsdorf I, Wedel A & Renkawitz R. Mouse lysozyme M gene: isolation, characterization, and expression studies. Proc Nat Acad Sci USA 1988; 85: 6232-6236.
34. Nunez V, Alameda D, Rico D, et al. Retinoid X receptor alpha controls innate inflammatory responses through the up-regulation of chemokine expression. Proc Nat Acad Sci USA 2010; 107: 10626-10631.
35. Du X, Tabeta K, Mann N, Crozat K, Mudd S & Beutler B. An essential role for Rxr alpha in the development of Th2 responses. Eur J Immunol 2005; 35: 3414-3423.
36. Szanto A, Narkar V, Shen Q, Uray IP, Davies PJ & Nagy L. Retinoid X receptors: X-ploring their (patho)physiological functions. Cell Death Differ 2004; 11(Suppl 2): S126-S143.
37. Lemotte PK, Keidel S & Apfel CM. Phytanic acid is a retinoid X receptor ligand. Eur J Biochem 1996; 236: 328-333.
38. Lengqvist J, Mata De Urquiza A, Bergman AC, et al. Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol Cell Proteomics 2004; 3: 692-703.
39. Haraguchi G, Suzuki J, Kosuge H, et al. A new RXR agonist, HX630, suppresses intimal hyperplasia in a mouse blood flow cessation model. J Mol Cell Cardiol 2006; 41: 885-892.
40. Kagechika H. Novel synthetic retinoids and separation of the pleiotropic retinoidal activities. Curr Med Chem 2002; 9: 591-608.
41. Kang SG, Wang C, Matsumoto S & Kim CH. High and low vitamin A therapies induce distinct FoxP3+ T-cell subsets and effectively control intestinal inflammation. Gastroenterology 2009; 137:1391-1402, e1391-1396.
42. Bai A, Lu N, Guo Y, Liu Z, Chen J & Peng Z. All-trans retinoic acid down-regulates inflammatory responses by shifting the Treg/Th17 profile in human ulcerative and murine colitis. J Leukoc Biol 2009; 86: 959-969.
43. Ricote M, Li AC, Willson TM, Kelly CJ & Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998; 391: 79-82.
44. Su CG, Wen X, Bailey ST, et al. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest 1999; 104: 383-389.
45. Desreumaux P, Dubuquoy L, Nutten S, et al. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer A basis for new therapeutic strategies. J Exp Med 2001; 193: 827-838.
46. Mora JR, Iwata M, Eksteen B, et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 2006; 314: 1157-1160.
47. Bjersing JL, Telemo E, Dahlgren U & Hanson LA. Loss of ileal IgA+ plasma cells and of CD4+ lymphocytes in ileal Peyer's patches of vitamin A deficient rats. Clin Exp Immunol 2002; 130: 404-408.
48. McDermott MR, Mark DA, Befus AD, Baliga BS, Suskind RM & Bienenstock J. Impaired intestinal localization of mesenteric lymphoblasts associated with vitamin A deficiency and protein-calorie malnutrition. Immunology 1982; 45: 1-5.
49. Wang JL, Swartz-Basile DA, Rubin DC & Levin MS. Retinoic acid stimulates early cellular proliferation in the adapting remnant rat small intestine after partial resection. J Nutr 1997; 127: 1297-1303.
50. Rojanapo W, Lamb AJ & Olson JA. The prevalence, metabolism and migration of goblet cells in rat intestine following the induction of rapid, synchronous vitamin A deficiency. J Nutr 1980; 110: 178-188.
51. Iwata M & Yokota A. Retinoic acid production by intestinal dendritic cells. Vitam Horm 2011; 86: 127-152.
52. Zile M, Bunge C & Deluca HF. Effect of vitamin A deficiency on intestinal cell proliferation in the rat. J Nutr 1977; 107: 552-560.
53. Osanai M, Nishikiori N, Murata M, Chiba H, Kojima T & Sawada N. Cellular retinoic acid bioavailability determines epithelial integrity: Role of retinoic acid receptor alpha agonists in colitis. Mol Pharmacol 2007; 71: 250-258.
54. Allen JE & Maizels RM. Diversity and dialogue in immunity to helminths. Nat Rev 2011; 11: 375-388.
55. Khan WI. Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model. Parasitology 2008; 135: 671-682.
56. Grencis RK, Else KJ, Huntley JF & Nishikawa SI. The in vivo role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice. Parasite Immunol 1993; 15: 55-59.
57. Carman JA, Pond L, Nashold F, Wassom DL & Hayes CE. Immunity to Trichinella spiralis infection in vitamin A-deficient mice. J Exp Med 1992; 175: 111-120.
58. Cantorna MT, Nashold FE & Hayes CE. In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function. J Immunol 1994; 152: 1515-1522.
59. Wiedermann U, Hanson LA, Kahu H & Dahlgren UI. Aberrant T-cell function in vitro and impaired T-cell dependent antibody response in vivo in vitamin A-deficient rats. Immunology 1993; 80: 581-586.
60. Hall JA, Cannons JL, Grainger JR, et al. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity 2011; 34: 435-447.
61. Nikawa T, Odahara K, Koizumi H, et al. Vitamin A prevents the decline in immunoglobulin A and Th2 cytokine levels in small intestinal mucosa of protein-malnourished mice. J Nutr 1999; 129: 934-941.
62. Carvalho CS, Melo EJ, Tenorio RP & Goes AJ. Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives. Braz J Med Biol Res 2009; 43: 139-149.
63. Mucida D, Park Y, Kim G, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007; 317: 256-260.
64. Sun CM, Hall JA, Blank RB, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 2007; 204: 1775-1785.
65. Chang SY, Cha HR, Chang JH, et al. Lack of retinoic acid leads to increased langerin-expressing dendritic cells in gut-associated lymphoid tissues. Gastroenterology 2009; 138:1468-1478, 1478.e1461-1466.
66. Gause WC, Urban JF, Jr & Stadecker MJ. The immune response to parasitic helminths: insights from murine models. Trends Immunol 2003; 24: 269-277.
67. Grainger JR, Smith KA, Hewitson JP, et al. Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-beta pathway. J Exp Med 2010; 207: 2331-2341.
68. Zaccone P, Burton OT, Gibbs SE, et al. The S. mansoni glycoprotein omega-1 induces Foxp3 expression in NOD mouse CD4 T cells. Eur J Immunol 2011; 41: 2709-2718.
69. Smith KA, Hochweller K, Hammerling GJ, Boon L, MacDonald AS & Maizels RM. Chronic helminth infection promotes immune regulation in vivo through dominance of CD11cloCD103- dendritic cells. J Immunol 2011; 186: 7098-7109.
70. Jaensson E, Uronen-Hansson H, Pabst O, et al. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 2008; 205: 2139-2149.
71. Mullaly SC, Burrows K, Antignano F & Zaph C. Assessing the role of CD103 in immunity to an intestinal helminth parasite. PLoS ONE 2011; 6: e19580.
72. Kennedy MW, Garside LH, Goodrick LE, et al. The Ov20 protein of the parasitic nematode Onchocerca volvulus A structurally novel class of small helix-rich retinol-binding proteins. J Biol Chem 1997; 272: 29442-29448.
73. Wolff KM & Scott AL. Brugia malayi: retinoic acid uptake and localization. Exp Parasitol 1995; 80: 282-290.
74. Kennedy MW, Brass A, McCruden AB, Price NC, Kelly SM & Cooper A. The ABA-1 allergen of the parasitic nematode Ascaris suum: fatty acid and retinoid binding function and structural characterization. Biochemistry 1995; 34: 6700-6710.
75. Fantappie MR, Freebern WJ, Osman A, LaDuca J, Niles EG & LoVerde PT. Evaluation of Schistosoma mansoni retinoid X receptor (SmRXR1 and SmRXR2) activity and tissue distribution. Mol Biochem Parasitol 2001; 115: 87-99.
76. Dawson H, Solano-Aguilar G, Beal M, et al. Localized Th1-, Th2-, T regulatory cell-, and inflammation-associated hepatic and pulmonary immune responses in Ascaris suum-infected swine are increased by retinoic acid. Infect Immun 2009; 77: 2576-2587.
77. Uematsu S, Fujimoto K, Jang MH, et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol 2008; 9: 769-776.
78. Tanumihardjo SA, Permaesih D, Muherdiyantiningsih E, et al. Vitamin A status of Indonesian children infected with Ascaris lumbricoides after dosing with vitamin A supplements and albendazole. The Journal of nutrition 1996; 126: 451-457.