The gut mucosal immune response to Toxoplasma gondii

Parasite Immunology

Volumn 37, Issue 3, 2015, Pages 108-117

  Cohen, S B ^a   Denkers, E Y ^a  

^a Department of Obstetrics Gynecology   (United States)

Author keywords

Host pathogen interactions; Intestinal mucosa; Toxoplasma gondii

Indexed keywords

CYTOKINE; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 1;

COMMENSAL; CYTOKINE RESPONSE; DENDRITIC CELL; HUMAN; ILEITIS; IMMUNE RESPONSE; IMMUNITY; IMMUNOPATHOLOGY; IMMUNOREGULATION; INFLAMMATORY BOWEL DISEASE; INTESTINE MUCOSA; LYMPHOCYTE; NONHUMAN; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; TH1 CELL; TOXOPLASMA GONDII; TOXOPLASMOSIS; ANIMAL; IMMUNOLOGY; MOUSE; MUCOSAL IMMUNITY; TOXOPLASMA;

MUS; TOXOPLASMA; TOXOPLASMA GONDII;

ANIMALS; HUMANS; IMMUNITY, MUCOSAL; INTESTINAL MUCOSA; LYMPHOCYTES; MICE; TOXOPLASMA; TOXOPLASMOSIS;

EID: 84923060802     PISSN: 01419838     EISSN: 13653024     Source Type: Journal    
DOI: 10.1111/pim.12164     Document Type: Review

References (103)

1. Egan CE, Cohen SB & Denkers EY. Insights into inflammatory bowel disease using Toxoplasma gondii as an infectious trigger. Immunol Cell Biol. Australasian Society for Immunology Inc 2012; 90: 668-675.
2. Schreiner M & Liesenfeld O. Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature. Mem Inst Oswaldo Cruz 2009; 104: 221-233.
3. Shao L, Serrano D & Mayer L. The role of epithelial cells in immune regulation in the gut. Semin Immunol 2001; 13: 163-176.
4. Ju C-H, Chockalingam A & Leifer CA. Early response of mucosal epithelial cells during Toxoplasma gondii infection. J Immunol 2009; 183: 7420-7427.
5. Clevers HC & Bevins CL. Paneth cells: maestros of the small intestinal crypts. Annu Rev Physiol 2013; 75: 289-311.
6. Kunisawa J, Takahashi I & Kiyono H. Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Immunol Rev 2007; 215: 136-153.
7. Cheroutre H, Lambolez F & Mucida D. The light and dark sides of intestinal intraepithelial lymphocytes. Nat Rev Immunol 2011; 11: 445-456.
8. Bekiaris V, Persson EK & Agace WW. Intestinal dendritic cells in the regulation of mucosal immunity. Immunol Rev 2014; 260: 86-101.
9. Sanos SL & Diefenbach A. Innate lymphoid cells: from border protection to the initiation of inflammatory diseases. Immunol Cell Biol 2013; 91: 215-224.
10. Cohen SB & Denkers EY. Border maneuvers: deployment of mucosal immune defenses against Toxoplasma gondii. Mucosal Immunol 2014; 7: 744-752.
11. Gazzinelli RT, Mendonça-Neto R, Lilue J, Howard J & Sher A. Innate resistance against Toxoplasma gondii: an evolutionary tale of mice, cats, and men. Cell Host Microbe 2014; 15: 132-138.
12. Yarovinsky F. Innate immunity to Toxoplasma gondii infection. Nat Rev Immunol 2014; 14: 109-121.
13. Gazzinelli RT, Wysocka M, Hayashi S, et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol 1994; 153: 2533-2543.
14. Denkers EY & Gazzinelli RT. Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev 1998; 11: 569-588.
15. Wilson DC, Grotenbreg GM, Liu K, et al. Differential regulation of effector- and central-memory responses to Toxoplasma gondii Infection by IL-12 revealed by tracking of Tgd057-specific CD8+ T cells. PLoS Pathog 2010; 6: e1000815.
16. Wilson DC, Matthews S & Yap GS. IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii Infection. J Immunol 2008; 180: 5935-5945.
17. Sturge CR & Yarovinsky F. Complex Immune Cell Interplay in the Gamma Interferon Response during Toxoplasma gondii Infection. Infect Immun 2014; 82: 3090-3097.
18. Scharton-Kersten TM, Wynn TA, Denkers EY, et al. In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection. J Immunol 1996; 157: 4045-4054.
19. Meredith MM, Liu K, Darrasse-Jeze G, et al. Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage. J Exp Med 2012; 209: 1153-1165.
20. Satpathy AT, KC W, Albring JC, et al. Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. J Exp Med 2012; 209: 1135-1152.
21. Pepper M, Dzierszinski F, Wilson E, et al. Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines. J Immunol 2008; 180: 6229-6236.
22. Varol C, Zigmond E & Jung S. Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria. Nat Rev Immunol 2010; 10: 415-426.
23. Edelson BT, KC W, Juang R, et al. Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med 2010; 207: 823-836.
24. Schiavoni G, Mattei F, Sestili P, et al. ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J Exp Med 2002; 196: 1415-1425.
25. Reis E, Sousa C, Hieny S, et al. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J Exp Med 1997; 186: 1819-1829.
26. Mashayekhi M, Sandau MM, Dunay IR, et al. CD8α(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity 2011; 35: 249-259.
27. Hall JA, Grainger JR, Spencer SP & Belkaid Y. The role of retinoic acid in tolerance and immunity. Immunity 2011; 35: 13-22.
28. 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.
29. Benson A, Pifer R, Behrendt CL, Hooper LV & Yarovinsky F. Gut commensal bacteria direct a protective immune response against Toxoplasma gondii. Cell Host Microbe 2009; 6: 187-196.
30. Sukhumavasi W, Egan CE, Warren AL, et al. TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite. J Immunol 2008; 181: 3464-3473.
31. Hand TW, Dos Santos LM, Bouladoux N, et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 2012; 337: 1553-1556.
32. Cohen SB, Maurer KJ, Egan CE, Oghumu S, Satoskar AR & Denkers EY. CXCR3-dependent CD4 T cells are required to activate inflammatory monocytes for defense against intestinal infection. PLoS Pathog 2013; 9: e1003706.
33. Dunay IR & Sibley LD. Monocytes mediate mucosal immunity to Toxoplasma gondii. Curr Opin Immunol 2010; 22: 461-466.
34. Serbina NV, Jia T, Hohl TM & Pamer EG. Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 2008; 26: 421-452.
35. Serbina NV & Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 2006; 7: 311-317.
36. Dunay IR, Damatta RA, Fux B, et al. Gr1(+) inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity 2008; 29: 306-317.
37. Schulthess J, Meresse B, Ramiro-Puig E, et al. Interleukin-15-dependent NKp46+ innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes. Immunity 2012; 37: 108-121.
38. Khan IA, Murphy PM, Casciotti L, et al. Mice lacking the chemokine receptor CCR1 show increased susceptibility to Toxoplasma gondii infection. J Immunol 2001; 166: 1930-1937.
39. Cai G, Kastelein R & Hunter CA. Interleukin-18 (IL-18) enhances innate IL-12-mediated resistance to Toxoplasma gondii. Infect Immun 2000; 68: 6932-6938.
40. Campanella GSV, Tager AM, El Khoury JK, et al. Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc Natl Acad Sci U S A 2008; 105: 4814-4819.
41. Rosas LE, Barbi J, Lu B, et al. CXCR3-/- mice mount an efficient Th1 response but fail to control Leishmania major infection. Eur J Immunol 2005; 35: 515-523.
42. Groom JR, Richmond J, Murooka TT, et al. CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity 2012; 37: 1091-1103.
43. Gazzinelli RT, Oswald IP, James SL & Sher A. IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages. J Immunol 1992; 148: 1792-1796.
44. Khan IA, Schwartzman JD, Matsuura T & Kasper LH. A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice. Proc Natl Acad Sci U S A 1997; 94: 13955-13960.
45. Bekpen C, Hunn JP, Rohde C, et al. The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage. Genome Biol 2005; 6: R92.
46. Hunn JP, Feng CG, Sher A & Howard JC. The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens. Mamm Genome 2011; 22: 43-54.
47. Howard JC, Hunn JP & Steinfeldt T. The IRG protein-based resistance mechanism in mice and its relation to virulence in Toxoplasma gondii. Curr Opin Microbiol 2011; 14: 414-421.
48. Khaminets A, Hunn JP, Könen-Waisman S, et al. Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole. Cell Microbiol 2010; 12: 939-961.
49. Liesenfeld O, Parvanova I, Zerrahn J, et al. The IFN-γ-inducible GTPase, Irga6, protects mice against Toxoplasma gondii but not against Plasmodium berghei and some other intracellular pathogens. PLoS ONE 2011; 6: e20568.
50. Degrandi D, Kravets E, Konermann C, et al. Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication. Proc Natl Acad Sci U S A 2013; 110: 294-299.
51. Haldar AK, Saka HA, Piro AS, et al. IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins. PLoS Pathog 2013; 9: e1003414.
52. Virreira Winter S, Niedelman W, Jensen KD, et al. Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS ONE 2011; 6: e24434.
53. Yamamoto M, Okuyama M, Ma JS, et al. A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii. Immunity 2012; 37: 302-313.
54. Denkers EY, Yap G, Scharton-Kersten T, et al. Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma gondii. J Immunol 1997; 159: 1903-1908.
55. Chardès T, Buzoni-Gatel D, Lepage A, Bernard F & Bout D. Toxoplasma gondii oral infection induces specific cytotoxic CD8 alpha/beta+ Thy-1+ gut intraepithelial lymphocytes, lytic for parasite-infected enterocytes. J Immunol 1994; 153: 4596-4603.
56. Buzoni-Gatel D, Debbabi H, Moretto M, et al. Intraepithelial lymphocytes traffic to the intestine and enhance resistance to Toxoplasma gondii oral infection. J Immunol 1999; 162: 5846-5852.
57. Lepage AC, Buzoni-Gatel D, Bout DT & Kasper LH. Gut-derived intraepithelial lymphocytes induce long term immunity against Toxoplasma gondii. J Immunol 1998; 161: 4902-4908.
58. Luangsay S, Kasper LH, Rachinel N, et al. CCR5 mediates specific migration of Toxoplasma gondii -primed CD8 lymphocytes to inflammatory intestinal epithelial cells. Gastroenterology 2003; 125: 491-500.
59. Buzoni-Gatel D, Lepage AC, Dimier-Poisson IH, Bout DT & Kasper LH. Adoptive transfer of gut intraepithelial lymphocytes protects against murine infection with Toxoplasma gondii. J Immunol 1997; 158: 5883-5889.
60. Liesenfeld O. Oral infection of C57BL/6 mice with Toxoplasma gondii: a new model of inflammatory bowel disease? J Infect Dis 2002; 185(Suppl 1): S96-S101.
61. Liesenfeld O, Kosek J, Remington JS & Suzuki Y. Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J Exp Med 1996; 184: 597-607.
62. Liesenfeld O, Kang H, Park D, et al. TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii. Parasite Immunol 1999; 21: 365-376.
63. Craven M, Egan CE, Dowd SE, et al. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn's disease. PLoS ONE 2012; 7: e41594.
64. Vossenkämper A, Struck D, Alvarado-Esquivel C, et al. Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol 2004; 34: 3197-3207.
65. Struck D, Frank I, Enders S, et al. Treatment with interleukin-18 binding protein ameliorates Toxoplasma gondii -induced small intestinal pathology that is induced by bone marrow cell-derived interleukin-18. Eur J Microbiol Immunol (Bp) 2012; 2: 249-257.
66. Lieberman LA, Cardillo F, Owyang AM, et al. IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12. J Immunol 2004; 173: 1887-1893.
67. Muñoz M, Heimesaat MM, Danker K, et al. Interleukin (IL)-23 mediates Toxoplasma gondii -induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J Exp Med 2009; 206: 3047-3059.
68. Wilson MS, Feng CG, Barber DL, et al. Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections. J Immunol 2010; 184: 4378-4390.
69. Guiton R, Vasseur V, Charron S, et al. Interleukin 17 receptor signaling is deleterious during Toxoplasma gondii infection in susceptible BL6 mice. J Infect Dis 2010; 202: 427-435.
70. Kelly MN, Kolls JK, Happel K, et al. Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun 2005; 73: 617-621.
71. Villeret B, Brault L, Couturier-Maillard A, et al. Blockade of IL-1R signaling diminishes Paneth cell depletion and Toxoplasma gondii induced ileitis in mice. Am J Clin Exp Immunol 2013; 2: 107-116.
72. Mennechet FJD, Kasper LH, Rachinel N, Li W, Vandewalle A & Buzoni-Gatel D. Lamina propria CD4+ T lymphocytes synergize with murine intestinal epithelial cells to enhance proinflammatory response against an intracellular pathogen. J Immunol 2002; 168: 2988-2996.
73. Egan CE, Craven MD, Leng J, Mack M, Simpson KW & Denkers EY. CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology during Toxoplasma gondii infection. Mucosal Immunol 2009; 2: 527-535.
74. Egan CE, Maurer KJ, Cohen SB, Mack M, Simpson KW & Denkers EY. Synergy between intraepithelial lymphocytes and lamina propria T cells drives intestinal inflammation during infection. Mucosal Immunol 2011; 4: 658-670.
75. Grainger JR, Wohlfert EA, Fuss IJ, et al. Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat Med 2013; 19: 713-721.
76. Benevides L, Milanezi CM, Yamauchi LM, Benjamim CF, Silva JS & Silva NM. CCR2 receptor is essential to activate microbicidal mechanisms to control Toxoplasma gondii infection in the central nervous system. Am J Pathol 2008; 173: 741-751.
77. Dunay IR, Fuchs A & Sibley LD. Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice. Infect Immun 2010; 78: 1564-1570.
78. Rosowski EE, Lu D, Julien L, et al. Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. J Exp Med 2011; 208: 195-212.
79. Butcher BA, Fox BA, Rommereim LM, et al. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog 2011; 7: e1002236.
80. Jensen KDC, Wang Y, Wojno EDT, et al. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. Cell Host Microbe 2011; 9: 472-483.
81. Jensen KDC, Hu K, Whitmarsh RJ, et al. Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15. Infect Immun 2013; 81: 2156-2167.
82. Gazzinelli RT, Wysocka M, Hieny S, et al. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12. IFN-gamma and TNF-alpha. J Immunol 1996; 157: 798-805.
83. Suzuki Y, Sher A, Yap G, et al. IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii. J Immunol 2000; 164: 5375-5382.
84. Roers A, Siewe L, Strittmatter E, et al. T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J Exp Med 2004; 200: 1289-1297.
85. Oldenhove G, Bouladoux N, Wohlfert EA, et al. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 2009; 31: 772-786.
86. Hall AO, Beiting DP, Tato C, et al. The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology. Immunity 2012; 37: 511-523.
87. Benson A, Murray S, Divakar P, et al. Microbial infection-induced expansion of effector T cells overcomes the suppressive effects of regulatory T cells via an IL-2 deprivation mechanism. J Immunol 2012; 188: 800-810.
88. Jankovic D, Kullberg MC, Feng CG, et al. Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 2007; 204: 273-283.
89. Neumann C, Heinrich F, Neumann K, et al. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J Exp Med 2014; 211(9): 1807-1819.
90. Buzoni-Gatel D, Debbabi H, Mennechet FJ, et al. Murine ileitis after intracellular parasite infection is controlled by TGF-beta-producing intraepithelial lymphocytes. Gastroenterology 2001; 120: 914-924.
91. Mennechet FJD, Kasper LH, Rachinel N, et al. Intestinal intraepithelial lymphocytes prevent pathogen-driven inflammation and regulate the Smad/T-bet pathway of lamina propria CD4+ T cells. Eur J Immunol 2004; 34: 1059-1067.
92. Nutsch KM & Hsieh C-S. T cell tolerance and immunity to commensal bacteria. Curr Opin Immunol 2012; 24: 385-391.
93. Raetz M, Hwang S-H, Wilhelm CL, et al. Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells. Nat Immunol 2013; 14: 136-142.
94. 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.
95. Minns LA, Menard LC, Foureau DM, et al. TLR9 is required for the gut-associated lymphoid tissue response following oral infection of Toxoplasma gondii. J Immunol 2006; 176: 7589-7597.
96. Heimesaat MM, Bereswill S, Fischer A, et al. Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. J Immunol 2006; 177: 8785-8795.
97. Economou M, Trikalinos TA, Loizou KT, Tsianos EV & Ioannidis JPA. Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 2004; 99: 2393-2404.
98. Brand S. Crohn"s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn"s disease. Gut 2009; 58: 1152-1167.
99. Hansen R, Thomson JM, El-Omar EM & Hold GL. The role of infection in the aetiology of inflammatory bowel disease. J Gastroenterol 2010; 45: 266-276.
100. Gevers D, Kugathasan S, Denson LA, et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 2014; 15: 382-392.
101. Wehkamp J, Salzman NH, Porter E, et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A 2005; 102: 18129-18134.
102. Billiet T, Rutgeerts P, Ferrante M, Van Assche G & Vermeire S. Targeting TNF-α for the treatment of inflammatory bowel disease. Expert Opin Biol Ther 2014; 14: 75-101.
103. Kostic AD, Xavier RJ & Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 2014; 146: 1489-1499.