Exploiting worm and allergy models to understand Th2 cytokine biology.
OBJECTIVE
Helminthic parasites and many allergens trigger highly polarized Th2-type immune responses. In most helminth infections, the Th2 response often leads to parasite expulsion or sequestration. During murine Schistosoma mansoni infection, however, the parasites persist and the chronic Th2 response induces severe pathological changes in the gut and liver. Thus, the study of schistosome infections in mice has become a popular model to study the pathogenesis of Th2 cytokine-mediated disease. This review will discuss recent findings from the schistosomiasis model that may be relevant to the understanding of allergic inflammation, asthma and Th2 cytokine biology in general.


RESULTS
Evidence is accumulating that the Th2 pathway is not a 'default pathway' but one that is actively instructed by mechanisms that are only beginning to be understood. Other areas of intensive investigation include studies on alternatively activated macrophages, the role of dendritic cells in Th2 response development, the inhibitory function of IL-10, regulatory T-cells and decoy receptors on chronic Th2-mediated inflammation, and the role of chitinases in mediating Th2 disease. Finally, the development of novel eosinophil-deficient mice has also accelerated our understanding of the contribution of this important cell type to Th2 immunity.


CONCLUSIONS
Many findings from the schistosomiasis model have been subsequently demonstrated in models of allergic disease, illustrating the utility of this model to dissect basic mechanisms of Th2-mediated inflammation. Further study of helminth-induced Th2 responses may expedite the discovery of new therapeutics for a wide range of Th2-associated diseases.
Ramalingam
Thirumalai R
TR
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Reiman
Rachael M
RM
Wynn
Thomas A
TA
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000469:parasitology; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000947:Antigens, Helminth; D016207:Cytokines