Trickle infection and immunity to Trichuris muris

English version

Autoři: Maya Glover ^aff001; Stefano A. P. Colombo ^aff001; David J. Thornton ^aff001; Richard K. Grencis ^aff001
Působiště autorů: Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom ^aff001; Wellcome Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom ^aff002
Vyšlo v časopise: Trickle infection and immunity to Trichuris muris. PLoS Pathog 15(11): e1007926. doi:10.1371/journal.ppat.1007926
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1007926

Souhrn

The majority of experiments investigating the immune response to gastrointestinal helminth infection use a single bolus infection. However, in situ individuals are repeatedly infected with low doses. Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected by a gradual increase in worm burden followed by partial expulsion. Flow cytometry revealed that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided with an increase in Type 2 cytokines. The development of resistance following trickle infection was associated with increased worm expulsion effector mechanisms including goblet cell hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells reversed resistance confirming their importance in protective immunity following trickle infection. In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following the development of resistance. These data establish trickle infection as a robust and informative model for analysis of immunity to chronic intestinal helminth infection more akin to that observed under natural infection conditions and confirms the importance of CD4+ T cell adaptive immunity in host protection.

Klíčová slova:

Helminth infections – Immune response – Microbiome – Nematode infections – Parasitic diseases – Parasitic intestinal diseases – T cells – Trichuriasis

Zdroje

1. Pullan RL, Smith JL, Jasrasaria R, Brooker SJ. Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasites and Vectors. 2014;7: 1–19. doi: 10.1186/1756-3305-7-1

2. Cooper PJ. Mucosal immunology of geohelminth infections in humans. Mucosal Immunol. 2009;2: 288–299. doi: 10.1038/mi.2009.14 19404245

3. Hotez PJ, Pearce EJ, Jacobson J, Hotez PJ, Brindley PJ, Bethony JM, et al. Helminth infections: the great neglected tropical diseases Find the latest version: Review series Helminth infections: the great neglected tropical diseases. J Clin Invest. 2008;118: 1311–1321. doi: 10.1172/JCI34261 18382743

4. Hotez PJ, Alvarado M, Basanez MG, Bolliger I, Bourne R, Boussinesq M, et al. The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases. PLoS Negl Trop Dis. 2014;8. doi: 10.1371/journal.pntd.0002865 25058013

5. Grencis RK. Immunity to Helminths: Resistance, Regulation, and Susceptibility to Gastrointestinal Nematodes. Annu Rev Immunol. 2015;33: 201–225. doi: 10.1146/annurev-immunol-032713-120218 25533702

6. Gerbe F, Sidot E, Smyth DJ, Ohmoto M, Matsumoto I, Dardalhon V, et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature. 2016;529: 226–230. doi: 10.1038/nature16527 26762460

7. Von Moltke J, Ji M, Liang HE, Locksley RM. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature. 2016;529: 221–225. doi: 10.1038/nature16161 26675736

8. Lavoie S, Michaud M, Tran S V., Margolskee RF, Gallini CA, Weinstock J V., et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science (80-). 2016;351: 1329–1333.

9. Ovington KS. Trickle infections of Nippostrongylus brasiliensis in rats. Z Parasitenkd. 1986;72: 851–853. doi: 10.1007/bf00925109 3799017

10. Brailsford TJ, Behnke JM. The dynamics of trickle infections with Ancylostoma ceylanicum in inbred hamsters. Parasitology. 1992;105 (Pt 2: 247–253.

11. Roach T.I.A.; Wakelin D.; Else K.J.; Bundy DA. Antigenic cross‐reactivity between the human whipworm, Trichuris trichiura, and the mouse trichuroids Trichuris muris and Trichinella spiralis. Parasite Immunol. 1988;10: 279–291. doi: 10.1111/j.1365-3024.1988.tb00221.x 3412784

12. Foth BJ, Tsai IJ, Reid AJ, Bancroft AJ, Nichol S, Tracey A, et al. Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction. Nat Genet. 2014;46: 693–700. doi: 10.1038/ng.3010 24929830

13. Else KJ, Grencis RK. Cellular immune responses to the murine nematode parasite Trichuris muris. I. Differential cytokine production during acute or chronic infection. Immunology. 1991;72: 508–13. 1903765

14. Cliffe LJ, Humphreys NE, Lane TE, Potten CS, Booth C, Grencis RK. Accelerated Intestinal Epithelial Cell Turnover: A New Mechanism of Parasite Expulsion Author(s): Laura J. Cliffe, Neil E. Humphreys, Thomas E. Lane, Chris S. Potten, Cath Booth and Richard K. Grencis Source: Science (80-). 2005;308: 1463–1465.

15. Bancroft AJ, McKenzie AN, Grencis RK. A critical role for IL-13 in resistance to intestinal nematode infection. J Immunol. 1998;160: 3453–61. 9531306

16. Cliffe LJ, Grencis RK. The Trichuris muris System: a Paradigm of Resistance and Susceptibility to Intestinal Nematode Infection. 2004;57: 255–307. doi: 10.1016/S0065-308X(04)57004-5 15504540

17. Hasnain SZ, Evans CM, Roy M, Gallagher AL, Kindrachuk KN, Barron L, et al. Muc5ac: a critical component mediating the rejection of enteric nematodes. J Exp Med. 2011;208: 893–900. doi: 10.1084/jem.20102057 21502330

18. Selby GR, Wakelin D. Transfer of immunity against Trichuris muris in the mouse by serum and cells. Int J Parasitol. 1973;3: 717–721. doi: 10.1016/0020-7519(73)90062-3 4762121

19. Else KJ, Grencis RK. Antibody-independent effector mechanisms in resistance to the intestinal nematode parasite Trichuris muris. Infect Immun. 1996;64: 2950–4. 8757819

20. Hasnain SZ, Dawson PA, Lourie R, Hutson P, Tong H, Grencis RK, et al. Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion. PLoS Pathog. 2017;13: 1–20. doi: 10.1371/journal.ppat.1006218 28192541

21. Houlden A, Hayes KS, Bancroft AJ, Worthington JJ, Wang P, Grencis RK, et al. Chronic Trichuris muris infection in C57BL/6 mice causes significant changes in host microbiota and metabolome: Effects reversed by pathogen clearance. PLoS One. 2015;10. doi: 10.1371/journal.pone.0125945 25938477

22. Holm JB, Sorobetea D, Kiilerich P, Ramayo-Caldas Y, Estellé J, Ma T, et al. Chronic Trichuris muris infection decreases diversity of the intestinal microbiota and concomitantly increases the abundance of lactobacilli. PLoS One. 2015;10: 1–22. doi: 10.1371/journal.pone.0125495 25942314

23. White EC, Houlden A, Bancroft AJ, Goldrick M, Hayes KS, Roberts IS, et al. Manipulation of host and parasite microbiotas: Survival strategies during chronic nematode infection. Sci Adv. 2018;4: eaap7399. doi: 10.1126/sciadv.aap7399 29546242

24. Hasnain SZ, McGuckin MA, Grencis RK, Thornton DJ. Serine Protease(s) Secreted by the Nematode Trichuris muris Degrade the Mucus Barrier. PLoS Negl Trop Dis. 2012;6. doi: 10.1371/journal.pntd.0001856 23071854

25. Hasnain SZ, Wang H, Ghia JE, Haq N, Deng Y, Velcich A, et al. Mucin Gene Deficiency in Mice Impairs Host Resistance to an Enteric Parasitic Infection. Gastroenterology. 2010;138: 1763–1771.e5. doi: 10.1053/j.gastro.2010.01.045 20138044

26. Artis D, Wang ML, Keilbaugh SA, He W, Brenes M, Swain GP, et al. RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract. Proc Natl Acad Sci U S A. 2004;101: 13596–600. doi: 10.1073/pnas.0404034101 15340149

27. Zaiss DM, Yang L, Shah PR, Kobie JJ, Urban JF, Mosmann TR. Amphiregulin, a T H 2 cytokine enhancing resistance to nematodes. Science (80-). 2006;314: 1746. doi: 10.1126/science.1133715 17170297

28. Pelly VS, Kannan Y, Coomes SM, Entwistle LJ, Rückerl D, Seddon B, et al. IL-4-producing ILC2s are required for the differentiation of TH2 cells following Heligmosomoides polygyrus infection. Mucosal Immunol. 2016. doi: 10.1038/mi.2016.4 26883724

29. Oliphant CJ, Hwang YY, Walker JA, Salimi M, Wong SH, Brewer JM, et al. MHCII-mediated dialog between group 2 innate lymphoid cells and CD4 + T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity. 2014;41: 283–295. doi: 10.1016/j.immuni.2014.06.016 25088770

30. Else KJ, Finkelman FD, Maliszewski CR, Grencis RK. Cytokine-mediated regulation of chronic intestinal helminth infection. J Exp Med. 1994;179: 347–351. doi: 10.1084/jem.179.1.347 8270879

31. Van Den Biggelaar AHJ, Van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, et al. Decreased atopy in children infected with Schistosoma haematobium: A role for parasite-induced interleukin-10. Lancet. 2000;356: 1723–1727. doi: 10.1016/S0140-6736(00)03206-2 11095260

32. Chico ME, Vaca MG, Rodriguez A, Cooper PJ. Soil-transmitted helminth parasites and allergy: Observations from Ecuador. Parasite Immunol. 2018; 1–11. doi: 10.1111/pim.12590 30229947

33. Mpairwe H, Amoah AS. Parasites and allergy: Observations from Africa. Parasite Immunol. 2018; 1–9. doi: 10.1111/pim.12589 30216486

34. Mohammed KA, Khamis IS, Lello J, Viney ME, Knopp S, Utzinger J. The relative contribution of co-infection to focal infection risk in children. Proc R Soc B Biol Sci. 2013;280: 20122813–20122813. doi: 10.1098/rspb.2012.2813 23303547

35. Behnke JM, Wakelin D, Wilson MM. Trichinella spiralis: Delayed rejection in mice concurrently infected with Nematospiroides dubius. Exp Parasitol. 1978;46: 121–130. doi: 10.1016/0014-4894(78)90162-5 743341

36. Jenkins SN, Behnke JM. Impairment of primary expulsion of trichuris muris in mice concurrently infected with nematospiroides dubius. Parasitology. 1977;75: 71–78. doi: 10.1017/s0031182000048332 593729

37. Behnke JM, Ali NMH, Jenkins SN. Survival to patency of low level infections with Trichuris muris in mice concurrently infected with Nematospiroides dubius. Ann Trop Med Parasitol. 1984;78: 509–517. doi: 10.1080/00034983.1984.11811857 6524995

38. Bancroft AJ, Else KJ, Humphreys NE, Grencis RK. The effect of challenge and trickle Trichuris muris infections on the polarisation of the immune response. Int J Parasitol. 2001;31: 1627–1637. doi: 10.1016/s0020-7519(01)00281-8 11730790

39. Bancroft AJ, Levy CW, Jowitt TA, Hayes KS, Thompson S, Mckenzie EA, et al. The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function. Nat Commun. 2019;10: 2344. doi: 10.1038/s41467-019-09996-z 31138806

40. Lee TDG, Wright KA. The morphology of the attachment and probable feeding site of the nematode Trichuris muris (Schrank, 1788) Hall, 1916. Can J Zool. 1978;56: 1889–1905. doi: 10.1139/z78-258 737601

41. Tilney LG, Connelly PS, Guild GM, Vranich KA, Artis D. Adaptation of a nematode parasite to living within the mammalian epithelium. J Exp Zool Part A Comp Exp Biol. 2005;303: 927–945. doi: 10.1002/jez.a.214 16217807

42. Betts J, deSchoolmeester ML, Else KJ. Trichuris muris: CD4+ T cell-mediated protection in reconstituted SCID mice. Parasitology. 2000;121 Pt 6: 631–7.

43. Betts CJ, Else KJ, Elisa M-. Mast cells are not critical in resistance to Trichuris muris. 1999; 45–52.

44. McCoy KD, Stoel M, Stettler R, Merky P, Fink K, Senn BM, et al. Polyclonal and Specific Antibodies Mediate Protective Immunity against Enteric Helminth Infection. Cell Host Microbe. 2008;4: 362–373. doi: 10.1016/j.chom.2008.08.014 18854240

45. Gerbe F, Legraverend C, Jay P. The intestinal epithelium tuft cells: Specification and function. Cell Mol Life Sci. 2012;69: 2907–2917. doi: 10.1007/s00018-012-0984-7 22527717

46. Owyang AM, Zaph C, Wilson EH, Guild KJ, McClanahan T, Miller HRP, et al. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med. 2006;203: 843–849. doi: 10.1084/jem.20051496 16606667

47. Klose CSN, Mahlakõiv T, Moeller JB, Rankin LC, Flamar AL, Kabata H, et al. The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature. 2017;549: 282–286. doi: 10.1038/nature23676 28869965

48. Maizels RM, Smits HH, McSorley HJ. Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity. 2018;49: 801–818. doi: 10.1016/j.immuni.2018.10.016 30462997

49. Lee SC, Tang MS, Lim YAL, Choy SH, Kurtz ZD, Cox LM, et al. Helminth Colonization Is Associated with Increased Diversity of the Gut Microbiota. PLoS Negl Trop Dis. 2014;8. doi: 10.1371/journal.pntd.0002880 24851867

50. Cooper P, Walker AW, Reyes J, Chico M, Salter SJ, Vaca M, et al. Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota. PLoS One. 2013;8. doi: 10.1371/journal.pone.0076573

51. Rosa BA, Supali T, Gankpala L, Djuardi Y, Sartono E, Zhou Y, et al. Differential human gut microbiome assemblages during soil-transmitted helminth infections in Indonesia and Liberia. Microbiome. 2018;6: 1–19. doi: 10.1186/s40168-017-0383-2

52. Alcantara-Neves NM, Veiga R V., Ponte JCM, Da Cunha SS, Simöes SM, Cruz ÁA, et al. Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children. PLoS One. 2017;12: 1–13. doi: 10.1371/journal.pone.0174089 28350867

53. Wilson MS, Taylor MD, Balic A, Finney CAM, Lamb JR, Maizels RM. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med. 2005;202: 1199–1212. doi: 10.1084/jem.20042572 16275759

54. Zaiss MM, Rapin A, Lebon L, Dubey LK, Mosconi I, Sarter K, et al. The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation. Immunity. 2015;43: 998–1010. doi: 10.1016/j.immuni.2015.09.012 26522986

55. Chenery AL, Antignano F, Burrows K, Scheer S, Perona-Wright G, Zaph C. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation. Infect Immun. 2016;84: 491–501. doi: 10.1128/IAI.01240-15 26644379

56. Kan SP. Soil-transmitted helminthiasis in Selangor, Malaysia. Med J Malaysia. 1982;37: 180–190. 7132839

57. Al-Delaimy AK, Al-Mekhlafi HM, Nasr NA, Sady H, Atroosh WM, Nashiry M, et al. Epidemiology of Intestinal Polyparasitism among Orang Asli School Children in Rural Malaysia. PLoS Negl Trop Dis. 2014;8. doi: 10.1371/journal.pntd.0003074 25144662

58. Raso G, Luginbühl A, Adjoua CA, Tian-Bi NT, Silué KD, Matthys B, et al. Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Côte d’Ivoire. Int J Epidemiol. 2004;33: 1092–1102. doi: 10.1093/ije/dyh241 15256525

59. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high- throughput community sequencing data Intensity normalization improves color calling in SOLiD sequencing. Nat Publ Gr. 2010;7: 335–336. doi: 10.1038/nmeth0510-335

60. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15: 550. doi: 10.1186/s13059-014-0550-8 25516281