Parasite black book

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A presentation derived from my literature review paper regarding the impact of parasites on host evolution and implications for medicine (e.g. considerations of helminth therapy for autoimmune disorders). Investigating the trigonometric interactions between parasites, hosts and microbiota is stressed because studying them in isolation will impede progress. The review also stresses the importance of perceiving the parasite-host relationship from the parasite's evolutionary perspective rather than focusing on the host's evolution.
  • 2. It’s Complicated… • Complicated relationship histories • Beyond “cops and robbers” • Impact on parasite-free humans
  • 3. The general who is skilled in defense hides in the most secret recesses of the earth
  • 4. Art of War: Concealment • Avoiding detection completely –Reside in tissues (e.g. brain) without immunosurveillance
  • 5. Numerical weakness comes from having to prepare against possible attacks; numerical strength, from compelling our adversary to make these preparations against us
  • 6. Art of War: Transience • Disappearing after detection –Motility –VSG (variant surface glycoprotein)
  • 7. VSG Shield Variant region Conserved region Membrane Ab Ab
  • 8. VSG Switch • Individual changes VSG expression • Adaptive immune response is against the common, old VSG • Individual with the new VSG survives and reproduces –Population is replenished
  • 9. VSG Nuclear Repositioning • Genes in designated regions are transcribed –Active VSG genes determined by position in nucleus
  • 10. The Switch
  • 11. The highest form of generalship is to balk the enemy’s plans…the next is to attack the enemy’s forces in the field
  • 12. Art of War: Subversion • Induce leukocyte apoptosis • Degrade C3 complement protein • Neutralize ROS attacks • Inhibit cytokine production
  • 13. Host Defenses • Innate and Acquired devices • Prostaglandins, leukotrienes & proteases • IL-22 • IgE –Opsonization –Antibody-dependent cell-mediated cytotoxicity
  • 14. Contain or Extirpate? • Hosts can eliminate parasites • But parasites make it exorbitantly expensive • Continuous parasitic presence
  • 15. If he sends reinforcements everywhere, he will everywhere be weak
  • 16. Competing Demands for Resources • Containment hypothesis –If containment is energetically favorable, then individuals that contain parasites will have greater reproductive success than those that eliminate them • Reproduction vs Immune System
  • 17. Parasites: Biological Ammunition • Invasion Advantage –Parasites can help migrants displace indigenous populations
  • 18. Evolutionary Stable Strategy • ESS- Once a strategy is exercised by enough individuals in a population, it (virtually) cannot be replaced • Individuals that optimally tolerate parasites outcompete those that either eradicate or succumb to them
  • 19. Background Check • Can parasites exert substantial evolutionary pressure? –Sickle cell heterozygote advantage • Have parasites impacted the evolution of the immune system? – Acquired immune system (AIS)
  • 20. miRNA Sabotage • Only sickle cell miRNAs prevent Plasmodium falciparum translation of metabolic proteins –Chimeric fusion of RNA
  • 21. AIS • Jawed vertebrate evolution parallels helminth diversification • γδ T cells prevalent in gut epithelium • Most selective pressure on gut- associated immunological genes
  • 22. Hygiene Hypothesis • Human immune system assumes parasite occupation • Parasite removal disrupts or destabilizes immune system –Autoimmunity and allergies
  • 23. Helminth Impact on Immune System • Elicit TH2 (allergic) response • Modulate TH1 (inflammatory )response • Elevate Treg (suppressive) response –IL-10 and TGF-β
  • 24. Helminths Sustain Balance
  • 25. Autoimmune Disorders and Allergies • Both virtually nonexistent in developing regions • Parasites can prevent onset of symptoms –e.g. Schistosoma mansoni treated type I diabetes, encephalomyelitis, collagen induced arthritis and Grave’s disease in mice
  • 26. IBD Clinical Trial • Inflammatory Bowel Disease treated with Trichuris suis • Greater than 70% remission rates • Chronically infected patients had lowest relapse rate
  • 27. Parasite Perspective • Dynamic –Experience selective pressures • Increase safety and efficacy of parasite- based treatments
  • 28. Intraspecific Competition • Progenesis peaked with second competitor –Pressure to outcompete • Progenesis plummeted with subsequent competitors –Resources too limited
  • 29. Interspecific Competition • Definitive host = final host • Intermediate host = in-between host • Parasite behavior may change if competitor shares definitive host
  • 30. Interspecific Competition cont. • C. Parvum progenesis –No change with A. galaxii (same definitive host) –Slight increase with Microphallus sp. (different definitive host) • Differential resource consumption –Microphallus sp. is smaller than A. galaxii
  • 31. The best thing of all is to take the enemy’s country whole and intact; to shatter and destroy it is not so good
  • 32. Virulence and Transmission • High virulence increases reproductive output • High transmission rates increases odds of reproductive success • Survival mechanisms can backfire by causing immunopathologies
  • 33. Subversion Tactics Mechanism Benefit (protection) Cost (host death) Superantigen expression Host suppresses immune response Systemic shock Major antigen production Protective inflammation Inflammatory disease Immune cell apoptosis Less resistance Septic shock
  • 34. Virulence and Transmission Balance • Negotiating virulence and transmission • Implications for parasite-based therapy –Immunosuppressive drugs should not be used because it removes stops for virulence
  • 35. We cannot enter into alliances until we are acquainted with the design of our neighbors
  • 36. Gut Microbiota • Bacteria and fungi that inhabit intestines • Mutualistic relationship with host –Provide Vitamin K and short-chain fatty acids –Inhibit pathogenesis –Receive nutrients and habitat
  • 37. Gut Microbiota cont. • Risks –Systemic shock if breach intestinal barriers –Dysbiosis (changes in community)
  • 38. Dysbiosis • High diversity and appropriate composition is healthy • Changes in community can lead to immunopathology –Disproportionate membership of pro- inflammatory bacteria • Host pressured to regulate microbiota
  • 39. Microbiota Coevolution • Comparable to parasites in pressure potential –Continuous presence • Containment approach
  • 40. Microbiota Impact on Immune System Evolution • Evolution of pathogen recognition receptors • IgA – Confines microbiota to outer mucosal layer • IL-22 • Monitor microbiota antigens • Disruptions of above induce dysbiosis
  • 41. Microbiota are Dynamic • Actively influence IgA secretion –Butyrate increases polymeric Ig receptor in epithelial cells, facilitating IgA secretion • Actively regulate IL-22 production • Stimulate host ILC1 cells to combat pathogenic bacteria
  • 42. Triumverate Host MicrobiotaParasite
  • 43. Trypanosoma cruzi Rhodnius prolixus Serratia marcescens
  • 44. Cruzi Studies: Physalin B • Host (insect) immune system suppressed via Physalin B • Microbiota burgeoned • Cruzi population declined
  • 45. Cruzi Studies: Physalin B cont. • Microbiota can combat parasites –Trypanolytic compounds –Reactive nitrogen species • Microbiota can ally with host –Sustained antiparasitic immune activity
  • 46. Cruzi Studies: Strains • Parasites combat microbiota to facilitate invasion • Dm38c strain –Antibacterial peptides –Phenoloxidase –Prolixicin
  • 47. Cruzi Studies: Strains cont. • Host treated with antibiotics –Dm38c strain established more prominent infection • Y strain –Does not colonize successfully –Vulnerable to microbiota-induced lysis • S. marcescens mannose-sensitive fimbriae
  • 48. Not Always East Side v West Side • Parasites and microbiota can benefit from each other’s presence –Parasitic development • H. polygyrus and T. muris –Opportunistic pathogen • T. suis infection helped Campylobacter expansion
  • 49. They CAN All Just Get Along • Macaques afflicted with idiopathic colitis • T. trichiura infection relieved symptoms and restored microbiota diversity • Buttresses hygiene hypothesis
  • 50. How to Predict Symbioses • Cost-benefit ratios of behavior –Individual (direct) –Neighbor (indirect) • Context –Environment –Evolutionary history
  • 51. Medical Implications • Deciphering the “little black book” is crucial • Parasite-based therapy efficacy and safety • Pathogenesis
  • 52. If you know the enemy and know yourself, you need not fear the result of a hundred battles  If you know yourself but not the enemy, for every victory gained you will also suffer a defeat  If you know neither the enemy nor yourself, you will succumb in every battle  Hence the saying:
  • 53. References Articles • Castro, D., C. Moraes, M. Gonzalez, I. Ribeiro, T. Tomassini, P. Azambuja, and E. Garcia. 2012 (a). Physalin B inhibits Trypanosoma cruzi infection in the gut of Rhodnius prolixus by affecting the immune system and microbiota. Journal of Insect Physiology, 58, 1620-1625. • Castro, D., C. Moraes, M. Gonzalez, N. Ratcliffe, P. Azambuja, and E. Garcia. 2012 (b). Trypanosoma cruzi immune response modulation decreases microbiota in Rhodnius prolixus gut and is crucial for parasite survival and development. PLoS ONE, 7(5), e36591. • Coleman, B., U. Ribacke, M. Manary, A. Bei., E. Winzeler, D. Wirth, and M. Duraisingh. 2012. Nuclear repositioning precedes promoter accessibility and is linked to switching frequency of a Plasmodium falciparum invasion gene. Cell Host & Microbe, 12, 739-750. • Cummings, M. S. Alexander and L. Oliveira, editors. 2009. Human Heredity 8th ed. Belmont (CA):Brooks/Cole. 245, 471 p. • Gráinne, H. and M. Boots. 2011. How can immunopathology shape the evolution of parasite virulence? Trends in Parasitology, 27 (7), 300-305. • Kaetzel, C. 2014. Cooperativity among secretory IgA, the polymeric immunoglobulin receptor, and the gut microbiota promotes host-microbial mutualism. Immunology Letters, • Khan, A. and P. Fallon. 2013. Helminth therapies: translating the unknown unknowns to known knowns. International Journal for Parasitology, 43, 293-299. • Kuo, C., V. Corby-Harris, and D. Promislow. 2008. The unavoidable costs and unexpected benefits of parasitism: population and metapopulation models of parasite-mediated competition. Journal of Theoretical Biology, 250, 244-256. • Lagrue, C., and R. Poulin. 2008. Intra- and interspecific competition among helminth parasites: effects on Coitocaecum parvum life history strategy, size and fecundity. International Journal for Parasitology, 38, 1435-1444. 10.1016/j.ijpara.2008.04.006. • LaMonte, G., N. Philip, J. Reardon, J. Lacsina, W. Majoros, L. Chapman, C. Thornburg, M. Telen, U. Ohler, C. Nicchitta, T. Haystead, and J. Chi. 2012. Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance. Cell Host & Microbe, 12, 187-189. • Leung, J. and P. Loke. 2013. A role for IL-22 in the relationship between intestinal helminths, gut microbiota and mucosal immunity. International Journal for Parasitology, 43, 253-257.
  • 54. References cont. • Murphy, K. J. Scobie editor. 2012. Janeway’s Immunobiology. London: Garland Science. 493-502 p. • Pays, E., S. Lips, D. Nolan, L. Vanhamme, and D. Pérez-Morga. 2001. The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts. Molecular & Biochemical Parasitology, 114, 1-16. • Rolff, J. 2007. Why did the acquired immune system of vertebrates evolve? Developmental and Comparative Immunology, 31, 476-482. • Sitjà-Bobadilla, A. 2008. Living off a fish: a trade-off between parasites and the immune system. Fish & Shellfish Immunology, 25, 358-372. • Stijlemans, B., K. Conrath, V. Cortez-Retamozo, H. Xong, L. Wyns, P. Senter, H. Revets., P. Baetselier, S. Myuldermans, and S. Magez. 2004. Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies: African tryapanosomes as paradigm. The Journal of Biological Chemistry, 279, 1256-1261. • Thaiss, C., M. Levy, J. Suez, and E. Elinav. 2014. The interplay between the innate immune system and the microbiota. Current Opinion in Immunology, 26, 41-48. • Zaccone, P. and A. Cooke. 2013. Vaccine against autoimmune disease: can helminths or their products provide a therapy. Current Opinion in Immunology, 25, 418-423.
  • 55. References cont. Quotations Tzu, Sun. 2011. Art of War. L. Giles translator. New York: Fall River. 5, 6, 9, 11, 12, 16, 20, 24, p. Additional Images Schwede, A., Jones, N., Engstler, M. and Carrington, M. 2011. The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes. Molecular and Biochemical Parasitology. 175 (2): 201-204
  • 56. Questions?
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