Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type-1 and type-2 cytokine-mediated inflammatory reactions

Development of polarized immune responses controls resistance and susceptib ility to many microorganisms. However, studies of several infectious, aller gic, and autoimmune diseases have shown that chronic type-1 and type-2 cyto kine responses can also cause significant morbidity and mortality if left u nchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal form s of liver pathology that develop in Schistosoma mansoni infected mice pola rized for type-1 and type-2 cytokine responses. Hierarchical clustering ana lysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis, apoptosis, and granulocyte recruitment an d activation generated by the microarray studies were confirmed later by tr aditional biological assays. The data show that cDNA microarrays are useful not only for determining coordinated gene expression profiles but are also highly effective for molecularly "fingerprinting" diseased tissues. Moreov er, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious disease pathogenesis.