A classification of tasks for the systematic study of immune response using functional genomics data.

A full understanding of the immune system and its responses to infection by different pathogens is important for the development of anti-parasitic vaccines. A growing number of large-scale experimental techniques, such as microarrays, are being used to gain a better understanding of the immune system. To analyse the data generated by these experiments, methods such as clustering are widely used. However, individual applications of these methods tend to analyse the experimental data without taking publicly available biological and immunological knowledge into account systematically and in an unbiased manner. To make best use of the experimental investment, to benefit from existing evidence, and to support the findings in the experimental data, available biological information should be included in the analysis in a systematic manner. In this review we present a classification of tasks that shows how experimental data produced by studies of the immune system can be placed in a broader biological context. Taking into account available evidence, the classification can be used to identify different ways of analysing the experimental data systematically. We have used the classification to identify alternative ways of analysing microarray data, and illustrate its application using studies of immune responses in mice to infection with the intestinal nematode parasites Trichuris muris and Heligmosomoides polygyrus.

Identification of novel genes in intestinal tissue that are regulated after infection with an intestinal nematode parasite.

Infection of resistant or susceptible mice with Trichuris muris provokes mesenteric lymph node responses which are polarized towards Th2 or Th1, respectively. These responses are well documented in the literature. In contrast, little is known about the local responses occurring within the infected intestine. Through microarray analyses, we demonstrate that the gene expression profile of infected gut tissue differs according to whether the parasite is expelled or not. Genes differentially regulated postinfection in resistant BALB/c mice include several antimicrobial genes, in particular, intelectin (Itln). In contrast, analyses in AKR mice which ultimately progress to chronic infection provide evidence for a Th1-dominated mucosa with up-regulated expression of genes regulated by gamma interferon. Increases in the expression of genes associated with tryptophan metabolism were also apparent with the coinduction of tryptophanyl tRNA synthetase (Wars) and indoleamine-2,3-dioxygenase (Indo). With the emerging literature on the role of these gene products in the suppression of T-cell responses in vitro and in vivo, their up-regulated expression here may suggest a role for tryptophan metabolism in the parasite survival strategy.