The immune response and immunopathology in infection with Schistosoma mansoni: a key role of major egg antigen Sm-p40.
The immune response and related granulomatous inflammation in infection with Schistosoma mansoni are ultimately dependent on SEA-sensitized CD4+ Th cells and comprise multiple pathways variously involving the activation and recruitment of different cell populations and the production of different inflammatory cytokines, all under the influence of regulatory genetic factors. The spontaneous downregulation of granuloma formation (immunomodulation), in turn, is a well-known phenomenon, but the full extent of its precipitating factors is still uncertain. This review describes a pathway leading to immunomodulation that features at its centre the down-regulatory cytokine IL-10. This mechanism is attractive because it offers a cogent correlation between findings in the laboratory and those displayed by patients affected with the disease. The Sm-p40 antigen, a major component of schistosome eggs, elicits a strong CD4+ Th cell response in H-2k mice that correlates with intense granuloma formation; in contrast, its immunogenicity is relatively minor during infection of other mouse strains that develop smaller granulomas. Of great interest is that the Sm-p40 antigen only elicits a Th-1 type cytokine response, a phenotype that remains constant even as the overall response to SEA shifts to a Th-2 type. The Sm-p40 molecule has a dominant epitope that is the target of CD4+ Th cells from infected H-2k mice; indeed, a minimal peptide that bears the epitope binds to I-Ak. The importance of pursuing a systematic elucidation of the major egg antigens, resides in the exciting possibility of specifically desensitizing the CD4+ Th cells that mediate granuloma formation, which may achieve meaningful prevention or amelioration of clinical disease.
Stadecker
M J
MJ
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Hernandez
H J
HJ
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015801:Helminth Proteins; D006801:Humans; D051379:Mice; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*
D000947:Antigens, Helminth; D015801:Helminth Proteins; C055560:p40 egg antigen, Schistosoma