title: Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response.
abstract: The control of strongyloidiasis affecting approximately 100 million people - caused by the gastrointestinal nematode Strongyloides stercoralis - is still based on anti-helminthic treatment. In the current study we analysed the immune response to Strongyloides ratti heat shock protein 60 (srHSP60) as a possible vaccine candidate in the murine system. We show that srHSP60 is a target of both, humoral and cellular response in S. ratti-infected mice. Strikingly, vaccination with srHSP60 without adjuvant or with CFA induced a S. ratti-specific Th1 response in vivo that did not confer protection but slightly increased larval output during challenge infection. Using in vitro T cell stimulation assays we provide further evidence that srHSP60 skewed activated T cells towards a Th1 response that interfered with efficient clearance of S. ratti infection. Vaccination with alum-precipitated srHSP60, in contrast, overruled the Th1-inducing activity intrinsic to srHSP60, induced a Th2 response, and conferred partial protection against a challenge infection. As srHSP60 is actively secreted by S. ratti during all life stages, our findings strongly suggest that srHSP60 induced polarization towards a Th1 response reflects a mechanism of immune evasion by this pathogenic nematode.
authors.affiliation: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht Str. 74, 20359 Hamburg, Germany.
authors.forename: Nadia Ben
authors.initials: NB
authors.lastname: Nouir
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Eschbach
authors.forename: Melanie
authors.initials: M
authors.lastname: Piédavent
authors.forename: Anke
authors.initials: A
authors.lastname: Osterloh
authors.forename: Manchang Tanyi
authors.initials: MT
authors.lastname: Kingsley
authors.forename: Klaus
authors.initials: K
authors.lastname: Erttmann
authors.forename: Norbert
authors.initials: N
authors.lastname: Brattig
authors.forename: Eva
authors.initials: E
authors.lastname: Liebau
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.forename: Minka
authors.initials: M
authors.lastname: Breloer
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D017170:Strongyloides ratti / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000947:Antigens, Helminth; D018834:Chaperonin 60; C041524:aluminum sulfate