Portal de Periódicos da CAPES

Nasal Administration of Schistosoma mansoni Egg Antigen‐Cholera B Subunit Conjugate Suppresses Hepatic Granuloma Formation and Reduces Mortality in S. mansoni ‐Infected Mice

2001; Wiley; Volume: 54; Issue: 5 Linguagem: Inglês

10.1046/j.1365-3083.2001.00977.x

1365-3083

Jie Sun, Miguel J. Stadecker, Nathalie Mielcarek, Mekuria Lakew, Bin‐Ling Li, Héctor J. Hernández, Cécil Czerkinsky, Jan Holmgren,

Hepatitis Viruses Studies and Epidemiology

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)‐γ, interleukin (IL)‐4 and IL‐5 production, together with an increase in transforming growth factor (TGF)‐β 1 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.