2. Defining relationships between humans and ascariasis Overview Prevalence Symptoms Ascarislifecycle Immunosuppressive activity Role of IL-10 Role of PAS-1 Hygiene hypothesis Evolution of the hypothesis and helminths Future implications
3. Ascariasis Most common helminth Infecting 25% of the world population Most prevalent in children Highest prevalence = 2 – 10 y/olds Highest intensity = 5 – 15 y/olds* Intensity due to co-infections
4. Warm, moist climates Bethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367, 1521-1532
12. Conflicting reports Reports indicating ascariasis Induced inflamatory response (AHR) Suppressed AHR Increased versus suppressed AHR More cases in which suppression occurs Novel genes provide insight… Maizels, R.M., et al. (2004). Helminth parasites—masters of regulation. Immunological Reviews; 201: 89-116.
13. Immunosuppressive activity 1977 discovery of MW of nematode allergen 10,000 – 50,000 MW 1986 expanded weight range components 14,000 – 410,000 MW Resulting in two distinct components Lower weight component (PIII) IgE-potentiating activity Higher weight component (PI) Protective antigen
14. Immunosuppressive activity In 1998 immunosuppression is confirmed For high molecular weight components (PI) Faquim-Mauro, E.L., & Macedo, M.S.. (1998). The immunosuppressive activity of Ascarissuum is due to highmolecular weight components. Clin Exp Immunol; 114: 245-251.
15. Cytokines In 2004, cytokines affected by Ascariswere starting to be confirmed. Th2 cytokines IL-4 IL-5 IL-10 Th1 cytokine IFN-gamma Cooper, P.J., Chico, M.E., Sandoval, C., & Nutman, T.B.. (2004). Atopic phenotype is an important determinant of immunoglobulin E-mediated inflammation and expression of T helper cell type 2 cytokines to Ascarisantigens in children exposed to Ascariasis. The Journal of Infectious Diseases; 190: 1338-1346.
16. Th1 and Th2 cytokines Romagnani, S.. (2004). The increased presence o fallergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?. Immunology; 112: 352-363.
17. Conditioned or Th2 like response Macedo, M.S., et al. (1998). Immumomudulation induced by Ascarissuum extract in mice: Effect of anti-interleukin-4 an inti-interleukin-10 andtibodies. Scand. J. Immunol; 47: 10-18
18. Protein component of A. suum In 2005, PAS-1 was a strong candidate as a suppressive protein component Oshiro, T.M., Macedo, M.S., & Macedo-Soares, M.F.. (2005). Anti-inflammatory activity of PAS-1, a protein component of Ascarissuum. Inflammation Research; 54: 17-21.
19. PAS-1 Further confirmed in 2006 Oshiro, T.M., et al. (2006). PAS-1, a protein affinity purified from Ascarissuum worms, maintains the ability to modulate the immune response to a bystander antigen. Immunology and Cell Biology; 84: 138-144.
20. The goal Using what we know It has been demonstrated that nullifying T-cell activity can “cure” chronic helminth infection. By allowing immune system to operate at full potential Are there trade-offs?
21. The hygiene hypothesis Much of what is known now is owed to this hypothesis ~1998 – present Although its definition has evolved…
22. By definition: A hypothesis that states that exposure to allergens in the environment early in life reduces the risk of developing allergies by boosting immune system activity. Conversely, relatively clean environment in early life would sway the immune system towards allergy-promoting responses.
23. Yasdanbakhsh, M., Kremsner, P.G., and van Ree, R.. (2002). Allergy, parasites, and the Hygiene Hypothesis. Science; 296: 490-494.
24. Before a “cure” We need to think about the trade off: Increase in chronic inflammatory diseases Like rheumatoid arthritis There should be consideration of controlling infections Much is yet to be learned as to the extent of control
25. Bibliography Working bibliography Altman, D.M.. (2008). Review on helminths, immune modulation and the hygiene hypothesis; Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology; 126: 1-2. Bethony, S.B., et al. (2006). Soil transmitted helminth infections: ascariaisis, trichuriasis, and hookworm. The lancet 2006; 367: 1521-1532. Carvalho, L., et al. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Mechanisms underlying helminth modulation of dendritic cell function. Immunology; 126: 1-2. Cooke, A.. (2008). Review series on helminthes, immune modulation and the hygiene hypothesi: How might infection mogulate the onset of type 1 diabetes?. Immunology; 126: 12-17. Cooper, P.J., Chico, M.E., Sandoval, C., & Nutman, T.B.. (2004). Atopic phenotype is an important determinant of immunoglobulin E-mediated inflammation and expression of T helper cell type 2 cytokines to Ascarisantigens in children exposed to Ascariasis. The Journal of Infectious Diseases; 190: 1338-1346. Crompton, D.W.T.. (2001). Ascarisand Ascariasis. Advances in Parasitology; 48: 285-375. Faquim-Mauro, E.L., & Macedo, M.S.. (1998). The immunosuppressive activity of Ascarissuum is due to high molecular weight components. Clin Exp Immunol; 114: 245-251. Fincham, J.E., et al. (2007). Ascaris, co-infection and allergy: the importance of analysis based on immunological variables rather than egg excretion. Transactions of the Royal Society of Tropical Medicine and Hygiene; 101: 680-682. Geha, R.S., Jabara, H.H., & Brodeur, S.R.. (2003). The regulation of immunoglogulin E class-switch recombination. Immunology; 3: 721-732. Haburchak, D.R.. (2008, September 12). Ascariasis. Emedicine. Retrieved September 18, 2009 from http://emedicine.medscape.com/article/212510 Hotez…Forgotten people, Forgotten diseases. Hogarth-Scott, R.S.. (1967). The molecular weight range of nematode allergens. Immunology; 13: 535-537. Itami, D.M., et al. (2005). Modulation of murine experimental asthma by Ascarissuumcomponents. Clinical and Experimental Allergy; 35: 873-879.
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Editor's Notes
There are two defined areas as to where ascaris comes in direct contact with mucosal linings. It is known that Treg cells can be preferentially induced at mucosal surfaces, in particular gut and respiratory tract. (32)
