Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response.
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Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response. / Nouir, Nadia Ben; Eschbach, Marie-Luise; Piedavent, Melanie; Osterloh, Anke; Kingsley, Manchang Tanyi; Erttmann, Klaus; Brattig, Norbert; Liebau, Eva; Fleischer, Bernhard; Breloer, Minka.
in: VACCINE, Jahrgang 30, Nr. 5, 5, 2012, S. 862-871.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Vaccination with Strongyloides ratti heat shock protein 60 increases susceptibility to challenge infection by induction of Th1 response.
AU - Nouir, Nadia Ben
AU - Eschbach, Marie-Luise
AU - Piedavent, Melanie
AU - Osterloh, Anke
AU - Kingsley, Manchang Tanyi
AU - Erttmann, Klaus
AU - Brattig, Norbert
AU - Liebau, Eva
AU - Fleischer, Bernhard
AU - Breloer, Minka
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Female
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Th1 Cells/immunology
KW - Adjuvants, Immunologic/administration & dosage
KW - Alum Compounds/administration & dosage
KW - Antigens, Helminth/administration & dosage/immunology/isolation & purification
KW - Chaperonin 60/administration & dosage/immunology/isolation & purification
KW - Disease Susceptibility
KW - Strongyloides ratti/immunology
KW - Strongyloidiasis/immunology/parasitology/prevention & control
KW - Th2 Cells/immunology
KW - Vaccination/methods
KW - Animals
KW - Female
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred C57BL
KW - Th1 Cells/immunology
KW - Adjuvants, Immunologic/administration & dosage
KW - Alum Compounds/administration & dosage
KW - Antigens, Helminth/administration & dosage/immunology/isolation & purification
KW - Chaperonin 60/administration & dosage/immunology/isolation & purification
KW - Disease Susceptibility
KW - Strongyloides ratti/immunology
KW - Strongyloidiasis/immunology/parasitology/prevention & control
KW - Th2 Cells/immunology
KW - Vaccination/methods
M3 - SCORING: Journal article
VL - 30
SP - 862
EP - 871
JO - VACCINE
JF - VACCINE
SN - 0264-410X
IS - 5
M1 - 5
ER -
