Harnessing the Helminth Secretome for Therapeutic Immunomodulators

BioMed Research International

Volumn 2014, Issue , 2014, Pages

  Ditgen, Dana ^a   Anandarajah, Emmanuela M ^a   Meissner, Kamila A ^b   Brattig, Norbert ^c   Wrenger, Carsten ^b   Liebau, Eva ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

^c BERNHARD NOCHT INSTITUTE FOR TROPICAL MEDICINE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EXCRETORY SECRETORY PRODUCT; HELMINTH PROTEIN; IMMUNOMODULATING AGENT; MICROBIAL PRODUCTS NOT CLASSIFIED ELSEWHERE; UNCLASSIFIED DRUG; IMMUNOLOGIC FACTOR;

BASOPHIL; CLINICAL TRIAL (TOPIC); CONTROLLED CLINICAL TRIAL (TOPIC); EOSINOPHIL; HELMINTH; HELMINTH SECRETOME; HELMINTHIASIS; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; MAST CELL; MICROBIAL MORPHOLOGY; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; THERAPY EFFECT; ANIMAL; IMMUNITY; IMMUNOLOGY; METABOLISM; PARASITE; PROTEOMICS; SECRETION (PROCESS);

VERMES;

ANIMALS; HELMINTH PROTEINS; HELMINTHS; IMMUNITY; IMMUNOLOGIC FACTORS; PARASITES; PROTEOMICS;

EID: 84929658785     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2014/964350     Document Type: Review

References (143)

1. J. Bach, "The effect of infections on susceptibility to autoimmune and allergic diseases, " The New England Journal of Medicine, vol. 347, no. 12, pp. 911-920, 2002.
2. D. E. Elliott and J. V. Weinstock, "Where are we on worms? Current Opinion in Gastroenterology, vol. 28, no. 6, pp. 551-556, 2012.
3. D. P. Strachan, "Hay fever, hygiene, and household size, " British Medical Journal, vol. 299, no. 6710, pp. 1259-1260, 1989.
4. P. J. Hotez, P. J. Brindley, J. M. Bethony, C. H. King, E. J. Pearce, and J. Jacobson, "Helminth infections: the great neglected tropical diseases, " Journal of Clinical Investigation, vol. 118, no. 4, pp. 1311-1321, 2008.
5. D. M. Altmann, "Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases, " Immunology, vol. 126, no. 1, pp. 1-2, 2009.
6. G. A. Rook, "Review series on helminths, immune modulation and the hygiene hypothesis: the broader implications of the hygiene hypothesis, " Immunology, vol. 126, no. 1, pp. 3-11, 2009.
7. M. Perband t, D. Ndjonka, and E. Liebau, "Protective mechanisms of helminths against reactive oxygen species are highly promising drug targets, " Current Medicinal Chemistry, vol. 21, no. 15, pp. 1794-1808, 2014.
8. R. Medzhitov, D. S. Schneider, and M. P. Soares, "Disease tolerance as a defense strategy, " Science, vol. 335, no. 6071, pp. 936-941, 2012.
9. S. D. Bilbo, G. A. Wray, S. E. Perkins, and W. Parker, "Reconstitution of the human biome as the most reasonable solution for epidemics of allergic and autoimmune diseases, " Medical Hypotheses, vol. 77, no. 4, pp. 494-504, 2011.
10. L. M. Kuijk and I. van Die, "Worms to the rescue: can worm glycans protect from autoimmune diseases? IUBMB Life, vol. 62, no. 4, pp. 303-312, 2010.
11. E. van Riet, F. C. Hartgers, and M. Yazdanbakhsh, "Chronic helminth infections induce immunomodulation: consequences and mechanisms, " Immunobiology, vol. 212, no. 6, pp. 475-490, 2007.
12. L. Carvalho, J. Sun, C. Kane, F. Marshall, C. Krawczyk, and E. J. Pearce, "Review series on helminths, immune modulation and the hygiene hypothesis: mechanisms underlying helminth modulation of dendritic cell function, " Immunology, vol. 126, no. 1, pp. 28-34, 2009.
13. J. A. Jackson, I. M. Friberg, S. Little, and J. E. Bradley, "Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology, vol. 126, no. 1, pp. 18-27, 2009.
14. R. M. Maizels and M. Yazdanbakhsh, "Immune regulation by helminth parasites: Cellular and molecular mechanisms, " Nature Reviews Immunology, vol. 3, no. 9, pp. 733-744, 2003.
15. L. J. Wang, Y. Cao, and H. N. Shi, "Helminth infections and intestinal inflammation, "World Journal of Gastroenterology, vol. 14, no. 33, pp. 5125-5132, 2008.
16. A. Rajamanickam and S. Babu, "Immunomodulation by filarial parasites, " International Trends in Immunity, vol. 1, no. 4, 2013.
17. C. A. Behm and K. S. Ovington, "The role of eosinophils in parasitic helminth infections: insights from genetically modified mice, " Parasitology Today, vol. 16, no. 5, pp. 202-209, 2000.
18. M. Yazdanbakhsh, P. G. Kremsner, and R. van Ree, "Immunology: allergy, parasites, and the hygiene hypothesis, " Science, vol. 296, no. 5567, pp. 490-494, 2002.
19. N. W. Brattig, F. W. Tischendorf, G. Strote, and C. E. Medina- De la Garza, "Eosinophil-larval-interaction in onchocerciasis: heterogeneity of in vitro adherence of eosinophils to infective third and fourth stage larvae and microfilariae of Onchocerca volvulus, " Parasite Immunology, vol. 13, no. 1, pp. 13-22, 1991.
20. M. P. Hübner, K. E. Killoran, M. Rajnik et al., "Chronic helminth infection does not exacerbateMycobacteriumtuberculosis infection, " PLoS Neglected Tropical Diseases, vol. 6, no. 12, Article ID e1970, 2012.
21. D. I. Pritchard, D. G. Blount, P. Schmid-Grendelmeier, and S. J. Till, "Parasitic worm therapy for allergy: is this incongruous or avant-garde medicine? Clinical and Experimental Allergy, vol. 42, no. 4, pp. 505-512, 2012.
22. M. P. Hübner, L. E. Layland , and A. Hoerauf, "Helminths and their implication in sepsis-a new branch of their immunomodulatory behaviour? Pathogens and Disease, vol. 69, no. 2, pp. 127-141, 2013.
23. K. J. Erb, C. Trujillo, M. Fugate, and H. Moll, "Infection with the helminth Nippostrongylus brasiliensis does not interfere with efficient elimination of Mycobacterium bovis BCG from the lungs of mice, " Clinical and Diagnostic Laboratory Immunology, vol. 9, no. 3, pp. 727-730, 2002.
24. F. G. Frantz, R. S. Rosada, W. M. Turato et al., "The immune response to toxocariasis does not modify susceptibility to Mycobacterium tuberculosis infection in BALB/c mice, " American Journal of Tropical Medicine and Hygiene, vol. 77, no. 4, pp. 691-698, 2007.
25. K. J. Erb, "Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases? Trends in Immunology, vol. 30, no. 2, pp. 75-82, 2009.
26. A. R. Khan and P. G. Fallon, "Helminth therapies: translating the unknown unknowns to known knowns, " International Journal for Parasitology, vol. 43, no. 3-4, pp. 293-299, 2013.
27. D. Larson, M. P. Hübner, M. N. Torrero et al., "Chronic helminth infection reduces basophil responsiveness in an IL- 10-dependent manner, " Journal of Immunology, vol. 188, no. 9, pp. 4188-4199, 2012.
28. E. Mitre, S. Norwood, and T. B. Nutman, "Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy, " Infection and Immunity, vol. 73, no. 7, pp. 4106-4111, 2005.
29. D. W. MacGlashan Jr., B. S. Bochner, D. C. Adelman et al., "Down-regulation of FceRI expression on human basophils during in vivo treatment of a topic patients with anti-IgE antibody, " Journal of Immunology, vol. 158, no. 3, pp. 1438-1445, 1997.
30. F. J. Malveaux, M. C. Conroy, N. F. Adkinson Jr., and L. M. Lichtenstein, "IgE receptors on human basophils. Relationship to serum IgE concentration, " Journal of Clinical Investigation, vol. 62, no. 1, pp. 176-181, 1978.
31. D. Larson, P. J. Cooper, M. P. Hübner et al., "Helminth infection is associated with decreased basophil responsiveness in human beings, " Journal of Allergy and Clinical Immunology, vol. 130, no. 1, pp. 270-272, 2012.
32. I. Ferreira, D. Smyth, S. Gaze et al., "Hookworm excretory/ secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ t cell responses and suppress pathology in a mousemodel of colitis, " Infection and Immunity, vol. 81, no. 6, pp. 2104-2111, 2013.
33. S. Babu and T. B. Nutman, "Immunopathogenesis of lymphatic filarial disease, " Seminars in Immunopathology, vol. 34, no. 6, pp. 847-861, 2012.
34. T. Adjobimey and A. Hoerauf, "Induction of immunoglobulin G4 in human filariasis: an indicator of immunoregulation, " Annals of Tropical Medicine and Parasitology, vol. 104, no. 6, pp. 455-464, 2010.
35. F. Mendlovic and A. Flisser, "Dendritic cells in the gut: interaction with intestinal helminths, " Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 250563, 10 pages, 2010.
36. C. Aranzamendi, F. Fransen, M. Langelaar et al., "Trichinella spiralis- secreted products modulate DC functionality and expand regulatory T cells in vitro, " Parasite Immunology, vol. 34, no. 4, pp. 210-223, 2012.
37. S. Navarro, I. Ferreira, and A. Loukas, "The hookworm pharmacopoeia for inflammatory diseases, " International Journal for Parasitology, vol. 43, no. 3-4, pp. 225-231, 2013.
38. B. Pulendran and D. Artis, "New paradigms in type 2 immunity, " Science, vol. 337, no. 6093, pp. 431-435, 2012.
39. J. Zhu, H. Yamane, and W. E. Paul, "Differentiation of effector CD4+ T cell populations, " Annual Review of Immunology, vol. 28, pp. 445-489, 2010.
40. W. E. Paul and J. Zhu, "How are TH2-type immune responses initiated and amplified? Nature Reviews Immunology, vol. 10, no. 4, pp. 225-235, 2010.
41. H. J. McSorley and R. M. Maizels, "Helminth infections and host immune regulation, " Clinical Microbiology Reviews, vol. 25, no. 4, pp. 585-608, 2012.
42. K. Mortimer, A. Brown, J. Feary et al., "Dose-ranging study for trials of therapeutic infection with Necator americanus in humans, " American Journal of Tropical Medicine and Hygiene, vol. 75, no. 5, pp. 914-920, 2006.
43. R. W. Summers, D. E. Elliott, K. Qadir, J. F. Urban Jr., R. Thompson, and J. V. Weinstock, "Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease, " American Journal of Gastroenterology, vol. 98, no. 9, pp. 2034-2041, 2003.
44. R. W. Summers, D. E. Elliot, J. F. Urban Jr., R. Thompson, and J. V. Weinstock, "Trichuris suis therapy in Crohns disease, " Gut, vol. 54, no. 1, pp. 87-90, 2005.
45. J. V. Weinstock, "Autoimmunity: the wormreturns, " Nature, vol. 491, no. 7423, pp. 183-185, 2012.
46. R. W. Summers, D. E. Elliott, J. F. Urban Jr., R. A. Thompson, and J. V. Weinstock, "Trichuris suis therapy for active ulcerative colitis: a rand omized controlled trial, "Gastroenterology, vol. 128, no. 4, pp. 825-832, 2005.
47. J. V. Weinstock and D. E. Elliott, "Translatability of helminth therapy in inflammatory bowel diseases, " International Journal for Parasitology, vol. 43, no. 3-4, pp. 245-251, 2013.
48. J. Croese, J. ONeil, J. Masson et al., "A proof of concept study establishing Necator americanus in Crohns patients and reservoir donors, " Gut, vol. 55, no. 1, pp. 136-137, 2006.
49. J. Correale and M. Farez, "Association between parasite infection and immune responses in multiple sclerosis, " Annals of Neurology, vol. 61, no. 2, pp. 97-108, 2007.
50. J. Correale and M. F. Farez, "The impactofparasite infections on the course of multiple sclerosis, " Journal of Neuroimmunology, vol. 233, no. 1-2, pp. 6-11, 2011.
51. M. Nacher, P. Singhasivanon, U. Silachamroon et al., "Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand , " The American Journal of Tropical Medicine and Hygiene, vol. 65, no. 6, pp. 834-836, 2001.
52. J. G. Fox, P. Beck, C. A. Dangler et al., "Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces Helicobacter-induced gastric atrophy, " Nature Medicine, vol. 6, no. 5, pp. 536-542, 2000.
53. P. G. Fallon and N. E. Mangan, "Suppression of TH2-type allergic reactions by helminth infection, " Nature Reviews Immunology, vol. 7, no. 3, pp. 220-230, 2007.
54. C. Wang, T. J. Nolan, G. A. Schad, and D. Abraham, "Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin, " Clinical & Experimental Allergy, vol. 31, no. 3, pp. 495-503, 2001.
55. A. Cooke, "Review series on helminths, immune modulation and the hygiene hypothesis: how might infection modulate the onset of type 1 diabetes? Immunology, vol. 126, no. 1, pp. 12-17, 2009.
56. G. Wohlleben, C. Trujillo, J. Müller et al., "Helminth infection modulates the development of allergen-induced airway inflammation, " International Immunology, vol. 16, no. 4, pp. 585-596, 2004.
57. R. Uchikawa, S. Matsuda, and N. Arizono, "Suppression of gamma interferon transcription and production by nematode excretory-secretory antigen during polyclonal stimulation of rat lymph node T cells, " Infection and Immunity, vol. 68, no. 11, pp. 6233-6239, 2000.
58. J. P. Hewitson, J. R. Grainger, and R. M. Maizels, "Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity, " Molecular and Biochemical Parasitology, vol. 167, no. 1, pp. 1-11, 2009.
59. A. Balic, Y. Harcus, M. J. Holland , and R. M. Maizels, "Selective maturation of dendritic cells by Nippostrongylus brasiliensissecreted proteins drives Th2 immune responses, " European Journal of Immunology, vol. 34, no. 11, pp. 3047-3059, 2004.
60. S. M. ONeill, M. T. Brady, J. J. Callanan et al., "Fasciola hepatica infection downregulates Th1 responses in mice, " Parasite Immunology, vol. 22, no. 3, pp. 147-155, 2000.
61. M. T. Brady, S. M. O'Neill, J. P. Dalton, and K. H. G. Mills, "Fasciola hepatica suppresses a protectiveTh1 response against Bordetella pertussis, " Infection and Immunity, vol. 67, no. 10, pp. 5372-5378, 1999.
62. J. P. Dalton, M. W. Robinson, G. Mulcahy, S. M. ONeill, and S. Donnelly, "Immunomodulatory molecules of Fasciola hepatica: cand idates for both vaccine and immunotherapeutic development, "Veterinary Parasitology, vol. 195, no. 3-4, pp. 272-285, 2013.
63. C. M. D. Miller, N. C. Smith, R. J. Ikin, N. R. Boulter, J. P. Dalton, and S. Donnelly, "Immunological interactions between 2 common pathogens, Th1-inducing protozoan Toxoplasma gondii and the Th2-inducing helminth fasciola hepatica, " PLoS ONE, vol. 4, no. 5, Article ID e5692, 2009.
64. A. Cooke, P. Tonks, F. M. Jones et al., "Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice, " Parasite Immunology, vol. 21, no. 4, pp. 169-176, 1999.
65. P. Zaccone, O. T. Burton, and A. Cooke, "Interplay of parasitedriven immune responses and autoimmunity, " Trends in Parasitology, vol. 24, no. 1, pp. 35-42, 2008.
66. A. Cooke, "Th17 cells in inflammatory conditions, " The Review of Diabetic Studies, vol. 3, no. 2, pp. 72-75, 2006.
67. H. H. Smits, B. Everts, F. C. Hartgers, and M. Yazdanbakhsh, "Chronic helminth infections protect against allergic diseases by active regulatory processes, " Current Allergy and Asthma Reports, vol. 10, no. 1, pp. 3-12, 2010.
68. C. J. Johnston, H. J. McSorley, S. M. and erton, S. J. Wigmore, and R. M. Maizels, "Helminths and immunological tolerance, " Transplantation, vol. 97, no. 2, pp. 127-132, 2014.
69. A. J. Daveson, D. M. Jones, S. Gaze et al., "Effect of hookworm infection on wheat challenge in celiac disease-a rand omised double-blinded placebo controlled trial, " PLoS ONE, vol. 6, no. 3, Article ID e17366, 2011.
70. C. Tilp, V. Kapur, W. Loging, and K. J. Erb, "Prerequisites for the pharmaceutical industry to develop and commercialise helminths and helminth-derived product therapy, " International Journal for Parasitology, vol. 43, no. 3-4, pp. 319-325, 2013.
71. P. Zaccone, Z. Feheérvári, F. M. Jones et al., "Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes, " European Journal of Immunology, vol. 33, no. 5, pp. 1439-1449, 2003.
72. A. Cooke, P. Zaccone, O. T. Burton et al., "Immune modulation by Schistosoma mansoni antigens in NOD mice: effects on both innate and adaptive immune systems, " Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 795210, 11 pages, 2010.
73. M. P. Hübner, J. T. Stocker, and E. Mitre, "Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells, " Immunology, vol. 127, no. 4, pp. 512-522, 2009.
74. M. J. G. Johnston, J. A. MacDonald, and D. M. McKay, "Parasitic helminths: a pharmacopeia of anti-inflammatory molecules, " Parasitology, vol. 136, no. 2, pp. 125-147, 2009.
75. N. E. Ruyssers, B. Y. DeWinter, J. G. DeMan et al., "Therapeutic potential of helminth soluble proteins in TNBS induced colitis in mice, " Inflammatory Bowel Diseases, vol. 15, no. 4, pp. 491-500, 2009.
76. M. W. Lightowlers and M. D. Rickard, "Excretory-secretory products of helminth parasites: effects on host immune responses, " Parasitology, vol. 96, supplement S1, pp. S123-S166, 1988.
77. V. Angeli, C. Faveeuw, P. Delerive et al., "Schistosoma mansoni induces the synthesis of IL-6 in pulmonary microvascular endothelial cells: role of IL-6 in the control of lung eosinophilia during infection, " European Journal of Immunology, vol. 31, no. 9, pp. 2751-2761, 2001.
78. R. R. White and K. Artavanis-Tsakonas, "How helminths use excretory secretory fractions to modulate dendritic cells, " Virulence, vol. 3, no. 7, pp. 668-677, 2012.
79. R. Shinya, H. Morisaka, T. Kikuchi, Y. Takeuchi, M. Ueda, and K. Futai, "Secretome analysis of the pine wood nematode bursaphelenchus xylophilus reveals the tangled roots of parasitism and its potential for molecular mimicry, " PLoS ONE, vol. 8, no. 6, Article ID e67377, 2013.
80. G. G. L. Cançado, J. A. Fiuza, N. C. N. de Paiva et al., "Hookworm products ameliorate dextran sodium sulfate-induced colitis in BALB/c mice, " Inflammatory Bowel Diseases, vol. 17, no. 11, pp. 2275-2286, 2011.
81. L. Du, H. Tang, Z. Ma et al., "The protective effect of the recombinant 53-kDa protein of Trichinella spiralis on experimental colitis in mice, " Digestive Diseases and Sciences, vol. 56, no. 10, pp. 2810-2817, 2011.
82. G. C. Hsieh, A. Loukas, A. M. Wahl et al., "A secreted protein from the human hookworm Necator americanus binds selectively to NK cells and induces IFN-γ production, " The Journal of Immunology, vol. 173, no. 4, pp. 2699-2704, 2004.
83. C. Schnoeller, S. Rausch, S. Pillai et al., "A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages, " Journal of Immunology, vol. 180, no. 6, pp. 4265-4272, 2008.
84. C. A. Terrazas, M. Alcantara-Hernandez, L. Bonifaz, L. I. Terrazas, and A. R. Satoskar, "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, "The FASEB Journal, vol. 27, no. 11, pp. 4547-4560, 2013.
85. A. Marcilla, M. Trelis, A. Cortés et al., "Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells, " PLoS ONE, vol. 7, no. 9, Article ID e45974, 2012.
86. G. S. Butler and C. M. Overall, "Proteomic identification of multitasking proteins in unexpected locations complicates drug targeting, " Nature Reviews Drug Discovery, vol. 8, no. 12, pp. 935-948, 2009.
87. M. E. Selkirk, O. Lazari, and J. B. Matthews, "Functional genomics of nematode acetylcholinesterases, " Parasitology, vol. 131, no. 1, pp. S3-S18, 2005.
88. U. andersson and K. J. Tracey, "Reflex principles of immunological homeostasis, " Annual Review of Immunology, vol. 30, pp. 313-335, 2012.
89. S. Bellafiore, Z. Shen, M. Rosso, P. Abad, P. Shih, and S. P. Briggs, "Direct identification of the Meloidogyne incognita secretome reveals proteins with host cell reprogramming potential, " PLoS Pathogens, vol. 4, no. 10, Article IDe1000192, 2008.
90. E. Roze, B. Hanse, M. Mitreva, B. Vanholme, J. Bakker, and G. Smant, "Mining the secretome of the root-knot nematode Meloidogyne chitwoodi for cand idate parasitism genes, " Molecular Plant Pathology, vol. 9, no. 1, pp. 1-10, 2008.
91. E. L. Davis, R. S. Hussey, T. J. Baumet al., "Nematode parasitism genes, " Annual Review of Phytopathology, vol. 38, no. 1, pp. 365-396, 2000.
92. X. Zang, M. Yazdanbakhsh, H. Jiang, M. R. Kanost, and R. M. Maizels, "A novel serpin expressed by blood-borne microfilariae of the parasitic nematode Brugia malayi inhibits human neutrophil serine proteinases, " Blood, vol. 94, no. 4, pp. 1418-1428, 1999.
93. X. Zang, A. K. Atmadja, P. Gray et al., "The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans, " Journal of Immunology, vol. 165, no. 9, pp. 5161-5169, 2000.
94. J. M. Dzik, "Molecules released by helminth parasites involved in host colonization, " Acta Biochimica Polonica, vol. 53, no. 1, pp. 33-64, 2006.
95. E. Liebau, J. Höppner, M. Mühlmeister et al., "The secretory omega-class glutathione transferase OvGST3 from the human pathogenic parasite Onchocerca volvulus, " The FEBS Journal, vol. 275, no. 13, pp. 3438-3453, 2008.
96. A. Sommer, R. Rickert, P. Fischer, H. Steinhart, R. D. Walter, and E. Liebau, "A dominant role for extracellular glutathione S-transferase from Onchocerca volvulus is the production of prostagland in D2, " Infection and Immunity, vol. 71, no. 6, pp. 3603-3606, 2003.
97. S. Nikolaou and R. B. Gasser, "Prospects for exploring molecular developmental processes in Haemonchus contortus, " International Journal for Parasitology, vol. 36, no. 8, pp. 859-868, 2006.
98. E. M. Schwarz, P. K. Korhonen, B. E. Campbell et al., "The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus, " Genome Biology, vol. 14, no. 8, article R89, 2013.
99. D. Knox, "Proteases in blood-feeding nematodes and their potential as vaccine cand idates, " in Cysteine Proteases of Pathogenic Organisms, vol. 712 of Advances in Experimental Medicine and Biology, pp. 155-176, Springer, New York, NY, USA, 2011.
100. J. H. McKerrow, C. Caffrey, B. Kelly, P. Loke, and M. Sajid, "Proteases in parasitic diseases, " Annual Review of Pathology, vol. 1, pp. 497-536, 2006.
101. C. J. Greenhalgh, A. Loukas, D. Donald, S. Nikolaou, and S. E. Newton, "A family of galectins from Haemonchus contortus, " Molecular and Biochemical Parasitology, vol. 107, no. 1, pp. 117-121, 2000.
102. D. H. Kim, R. Feinbaum, G. Alloing et al., "A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity, " Science, vol. 297, no. 5581, pp. 623-626, 2002.
103. R. M. Maizels, N. Gomez-Escobar, W. F. Gregory, J. Murray, and X. Zang, "Immune evasion genes from filarial nematodes, " International Journal for Parasitology, vol. 31, no. 9, pp. 889-898, 2001.
104. T. Calandra and T. Roger, "Macrophage migration inhibitory factor: a regulator of innate immunity, " Nature Reviews Immunology, vol. 3, no. 10, pp. 791-800, 2003.
105. F. H. Falcone, P. Loke, X. Zang, A. S. MacDonald, R. M. Maizels, and J. E. Allen, "A Brugia malayi homolog of macrophage migration inhibitory factor reveals an important link between macrophages and eosinophil recruitment during nematode infection, " The Journal of Immunology, vol. 167, no. 9, pp. 5348-5354, 2001.
106. L. Prieto-Lafuente, W. F. Gregory, J. E. Allen, and R. M. Maizels, "MIF homologues from a filarial nematode parasite synergize with IL-4 to induce alternative activation of hostmacrophages, " Journal of Leukocyte Biology, vol. 85, no. 5, pp. 844-854, 2009.
107. J. Rzepecka, S. Rausch, C. Klotz et al., "Calreticulin from the intestinal nematode Heligmosomoides polygyrus is a Th2- skewing protein and interacts with murine scavenger receptor- A, " Molecular Immunology, vol. 46, no. 6, pp. 1109-1119, 2009.
108. J. P. Hewitson, A. C. Ivens, Y. Harcus et al., "Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity, " PLoS Pathogens, vol. 9, no. 8, Article ID e1003492, 2013.
109. A. Loukas, M. Hintz, D. Linder et al., "A family of secreted mucins from the parasitic nematode Toxocara canis bears diverse mucin domains but shares similar flanking six-cysteine repeat motifs, " The Journal of Biological Chemistry, vol. 275, no. 50, pp. 39600-39607, 2000.
110. V. Chi, M. W. Pennington, R. S. Norton et al., "Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases, " Toxicon, vol. 59, no. 4, pp. 529-546, 2012.
111. A. R. Jex, S. Liu, B. Li et al., "Ascaris suum draft genome, " Nature, vol. 479, no. 7374, pp. 529-533, 2011.
112. F. N. Karanu, F. R. Rurangirwa, T. C. McGuire, and D. P. Jasmer, "Haemonchus contortus: identification of proteases with diverse characteristics in adult worm excretory-secretory products, " Experimental Parasitology, vol. 77, no. 3, pp. 362-371, 1993.
113. A. L. Williamson, S. Lustigman, Y. Oksov et al., "Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration, " Infection and Immunity, vol. 74, no. 2, pp. 961-967, 2006.
114. C. A. A. de Araújo, A. Perini, M. A. Martins, M. S. Macedo, and M. F. Macedo-Soares, " PAS-1, an ascaris suum protein, modulates allergic airway inflammation via CD8+ γδTCR+ and CD4+ CD25+ FoxP3+ T Cells, " Scandinavian Journal of Immunology, vol. 72, no. 6, pp. 491-503, 2010.
115. Y. Furuhashi, S. Imai, H. Tezuka, and K. Fujita, "Recombinant Dirofilaria immitis-derived antigen can suppress passive cutaneous anaphylaxis reactions, " International Archives of Allergy and Immunology, vol. 125, no. 2, pp. 144-151, 2001.
116. N. Borchert, C. Becker-Pauly, A. Wagner, P. Fischer, W. Stöcker, and N. W. Brattig, "Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus, " Microbes and Infection, vol. 9, no. 4, pp. 498-506, 2007.
117. S. K. Smith, A. J. Nisbet, L. I. Meikle et al., "Proteomic analysisof excretory/secretory products released by Teladorsagia circumcincta larvae early post-infection, " Parasite Immunology, vol. 31, no. 1, pp. 10-19, 2009.
118. N. S. Prasanphanich, M. L. Mickum, J. Heimburg-Molinaro, and R. D. Cummings, "Glycoconjugates in host-helminth interactions, " Frontiers in immunology, vol. 4, p. 240, 2013.
119. W. Harnett and M. M. Harnett, "Modulation of the host immune system by phosphorylcholine-containing glycoproteins secreted by parasitic filarial nematodes, " Biochimica et Biophysica Acta. Molecular Cell Research, vol. 1539, no. 1-2, pp. 7-15, 2001.
120. J. Grabitzki and G. Lochnit, "Immunomodulation by phosphocholine- Biosynthesis, structures and immunological implications of parasitic PC-epitopes, " Molecular Immunology, vol. 47, no. 2-3, pp. 149-163, 2009.
121. W. Harnett and M. M. Harnett, "Molecular basis of worminduced immunomodulation, " Parasite Immunology, vol. 28, no. 10, pp. 535-543, 2006.
122. W. Harnett, I. B. McInnes, and M. M. Harnett, "ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential, " Immunology Letters, vol. 94, no. 1-2, pp. 27-33, 2004.
123. M. M. Harnett, D. E. Kean, A. Boitelle et al., "The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis, " Annals of the Rheumatic Diseases, vol. 67, no. 4, pp. 518-523, 2008.
124. H. Zhang, X. Li, D. B. Martin, and R. Aebersold, "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry, " Nature Biotechnology, vol. 21, no. 6, pp. 660-666, 2003.
125. Y. Moreno and T. G. Geary, "Stage- and gender-specific proteomic analysis of Brugia malayi excreto-secretory products, " PLoS Neglected Tropical Diseases, vol. 2, no. 10, article e326, 2008.
126. J. P. Hewitson, Y. M. Harcus, R. S. Curwen et al., "The secretome of the filarial parasite, Brugia malayi: proteomic profile of adult excretory-secretory products, "Molecular and Biochemical Parasitology, vol. 160, no. 1, pp. 8-21, 2008.
127. S. Bennuru, R. Semnani, Z. Meng, J. M. C. Ribeiro, T. D. Veenstra, and T. B. Nutman, "Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and genderspecific proteomic profiling, " PLoS Neglected Tropical Diseases, vol. 3, no. 4, article e410, 2009.
128. J. Geary, M. Satti, Y. Moreno et al., "First analysis of the secretome of the canine heartworm, Dirofilaria immitis, " Parasites & Vectors, vol. 5, article 140, no. 1, 2012.
129. J. Mulvenna, B. Hamilton, S. H. Nagaraj, D. Smyth, A. Loukas, and J. J. Gorman, "Proteomics analysis of the excretory/ secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum, " Molecular and Cellular Proteomics, vol. 8, no. 1, pp. 109-121, 2009.
130. H. Saverwyns, A. Visser, A. J. Nisbet et al., "Identification and characterization of a novel specific secreted protein family for selected members of the subfamily Ostertagiinae (Nematoda), " Parasitology, vol. 135, no. 1, pp. 63-70, 2008.
131. I. Vercauteren, P. Geldhof, I. Peelaers, E. Claerebout, G. Berx, and J. Vercruysse, "Identification of excretory-secretory products of larval and adult Ostertagia ostertagi by immunoscreening of cDNA libraries, "Molecular and Biochemical Parasitology, vol. 126, no. 2, pp. 201-208, 2003.
132. G. Garg and S. Ranganathan, "In silico secretome analysis approach for next generation sequencing transcriptomic data, " BMC Genomics, vol. 12, supplement 3, article S14, 2011.
133. H. Soblik, A. E. Younis, M. Mitreva et al., "Life cycle stageresolved proteomic analysis of the excretome/secretome from Strongyloides ratti-identification of stage-specific proteases, " Molecular & Cellular Proteomics: MCP, vol. 10, no. 12, Article ID M111.010157, 2011.
134. H. Craig, J. M. Wastling, and D. P. Knox, "A preliminary proteomic survey of the in vitro excretory/secretory products of fourth-stage larval and adult Teladorsagia circumcincta, " Parasitology, vol. 132, no. 4, pp. 535-543, 2006.
135. M. W. Robinson, R. Greig, K. A. Beattie, D. J. Lamont, and B. Connolly, "Comparative analysis of the excretory-secretory proteome of the muscle larva of Trichinella pseudospiralis and Trichinella spiralis, " International Journal for Parasitology, vol. 37, no. 2, pp. 139-148, 2007.
136. M. W. Robinson and B. Connolly, "Proteomic analysis of the excretory-secretory proteins of the Trichinella spiralis L1 larva, a nematode parasite of skeletal muscle, " Proteomics, vol. 5, no. 17, pp. 4525-4532, 2005.
137. D. Bernal, M. Trelis, S. Montaner et al., "Surface analysis of Dicrocoelium dendriticum the molecular characterization of exosomes reveals the presence of miRNAs, " Journal of Proteomics, vol. 105, pp. 232-241, 2014.
138. A. M. Martínez-Ibeas, C. González-Lanza, and M. Y. Manga- González, "Proteomic analysis of the tegument and excretorysecretory products of Dicrocoeliumdendriticum(digenea) adult worms, " Experimental Parasitology, vol. 133, no. 4, pp. 411-420, 2013.
139. B. E. F. Gourbal, F. Guillou, G. Mitta et al., "Excretory-secretory products of larval Fasciola hepatica investigated using a twodimensional proteomic approach, " Molecular and Biochemical Parasitology, vol. 161, no. 1, pp. 63-66, 2008.
140. M. W. Robinson, R. Menon, S. M. Donnelly, J. P. Dalton, and S. Ranganathan, "An integrated transcriptomics and proteomics analysis of the secretome of the helminth pathogen Fasciola hepatica: proteins associated with invasion and infection of the mammalian host, "Molecular and Cellular Proteomics, vol. 8, no. 8, pp. 1891-1907, 2009.
141. G. M. Knudsen, K. F. Medzihradszky, K. Lim, E. Hansell, and J. H. McKerrow, "Proteomic analysis of Schistosoma mansoni cercarial secretions, " Molecular and Cellular Proteomics, vol. 4, no. 12, pp. 1862-1875, 2005.
142. E. Hansell, S. Braschi, K. F. Medzihradszky et al., "Proteomic analysis of skin invasion by blood fluke larvae, " PLoS Neglected Tropical Diseases, vol. 2, no. 7, article e262, 2008.
143. C. L. Cass, J. R. Johnson, L. L. Califf et al., "Proteomic analysis of Schistosoma mansoni egg secretions, " Molecular and Biochemical Parasitology, vol. 155, no. 2, pp. 84-93, 2007.