title: Integrated analysis of innate, Th1, Th2, Th17, and regulatory cytokines identifies changes in immune polarisation following treatment of human schistosomiasis.
abstract: BACKGROUND
  Schistosomiasis elicits cross-regulatory immune responses, but it is unclear how antihelminthic treatment affects this balance. This study integrates data on 13 cytokines elicited by 3 schistosome to examine how praziquantel treatment alters immune polarization and whether post-treatment cytokine profiles influence reinfection status.
  
  
  METHODS
  Venous blood from 72 Schistosoma haematobium-exposed participants was cultured with schistosome egg, adult worm, and cercaria antigens pre- and 6 weeks post-praziquantel treatment. Innate inflammatory (tumor necrosis factor α [TNF-α], interleukin(IL-)-6, IL-8), Th1 (interferon γ [IFN-γ], IL-2, IL-12p70), Th2 (IL-4, IL-5, IL-13), Th17 (IL-17A, IL-21, IL-23p19), and regulatory (IL-10) cytokines were quantified via enzyme-linked immunosorbent assay. Cytokine data was integrated using nonmetric multidimensional scaling and factor analysis.
  
  
  RESULTS
  Egg-specific cytokine phenotypes became more proinflammatory post-treatment due to increased TNF-α, IL-6, IL-8, IFN-γ, IL-12p70, and IL-23 levels. Post-treatment cercariae-specific responses were also more proinflammatory reflecting elevated IL-8. In contrast, post-treatment adult worm-specific responses were less inflammatory, reflecting lower post-treatment IL-6. A combination of egg-induced IL-6, IL-12p70, IL-21, and IL-23 and adult worm-induced IL-5 and IL-21 post-treatment was associated with reduced reinfection risk 18 months later.
  
  
  CONCLUSIONS
  Praziquantel treatment markedly alters polarization of schistosome-specific cytokine responses, and these changes, particularly in response to egg-stage parasites, may promote resistance to reinfection.
authors.affiliation: Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, United Kingdom. claire.bourke@york.ac.uk
authors.forename: Claire D
authors.initials: CD
authors.lastname: Bourke
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.forename: Nadine
authors.initials: N
authors.lastname: Rujeni
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Appleby
authors.forename: Kate M
authors.initials: KM
authors.lastname: Mitchell
authors.forename: Nicholas
authors.initials: N
authors.lastname: Midzi
authors.forename: Takafira
authors.initials: T
authors.lastname: Mduluza
authors.forename: Francisca
authors.initials: F
authors.lastname: Mutapi
mesh_terms: D000293:Adolescent; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D053759:Interleukin-23 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D011223:Praziquantel / Q000627:therapeutic use*; D012548:Schistosoma haematobium / Q000276:immunology; D012552:Schistosomiasis / Q000188:drug therapy / Q000276:immunology*; D012553:Schistosomiasis haematobia / Q000188:drug therapy / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000098546:Interleukin-21
chemical_list: D000871:Anthelmintics; D016207:Cytokines; D018793:Interleukin-13; D020381:Interleukin-17; D007376:Interleukin-2; D053759:Interleukin-23; D015848:Interleukin-5; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D011223:Praziquantel; D007371:Interferon-gamma; D000098546:Interleukin-21