Nasal administration of Schistosoma mansoni egg antigen-cholera B subunit conjugate suppresses hepatic granuloma formation and reduces mortality in S. mansoni-infected mice.
Granulomatous inflammation in schistosomiasis is a delayed-type hypersensitivity reaction mediated by CD4+ T cells specific for parasite egg antigens (Ags). In an attempt to control T-cell responses leading to excessive harmful inflammation and granuloma formation, especially in the liver, BALB/c mice were intranasally (i.n.) treated with soluble Schistosoma mansoni egg Ags (SEA) conjugated to cholera toxin B subunit (CTB), a mucosa-binding protein with demonstrated capacity to suppress inflammatory T-cell functions after mucosal administration. Treatment with CTB-SEA significantly conjugate a reduced liver granuloma formation in infected mice associated with decreased SEA specific Th1- and Th2-type immune responses by liver leukocytes. Importantly, treatment with CTB-SEA conjugate also significantly reduced the mortality in chronically infected mice. In S. mansoni-infected large-granuloma forming CBA mice, i.n. treatment with purified Sm-p40, the major egg antigen, conjugated to CTB likewise significantly inhibited hepatic egg granuloma formation. A reduction of SEA-driven lymphoproliferation and of interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 production, together with an increase in transforming growth factor (TGF)-beta1 production, were observed in splenic cells from CTB-Sm-p40-treated SEA-sensitized mice, as well as in liver leukocytes from CTB-Sm-p40-treated schistosome-infected mice. These results indicate that mucosal administration of SEA or purified Sm-p40 antigen in conjunction with CTB is highly effective in curtailing immunopathologic manifestations of schistosomiasis in vivo in infected hosts.
Sun
J B
JB
Department of Medical Microbiology and Immunology, University of Göteborg, Guldhedsgatan 10 A, SE-413 46 Göteborg, Sweden. jia-bin.sun@microbio.gu.se
Stadecker
M J
MJ
Mielcarek
N
N
Lakew
M
M
Li
B L
BL
Hernandez
H J
HJ
Czerkinsky
C
C
Holmgren
J
J
D000281:Administration, Intranasal; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage*; D002772:Cholera Toxin / Q000008:administration & dosage; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015801:Helminth Proteins; D018928:Immunity, Mucosal; D008099:Liver / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010063:Ovum / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage
D000947:Antigens, Helminth; D015801:Helminth Proteins; D018074:Vaccines, Conjugate; C055560:p40 egg antigen, Schistosoma; D002772:Cholera Toxin