Microarrays can indicate costs of immunity

In many of the transcriptomic experiments, gene expression is measured along a time course after infection to include various stages of the immune response. In addition to the putative immunity genes, this can also provide information on genes that reflect the costs of launching an immune response.

Most genes with differential expression after parasitoid attack were not exclusively expressed (or switched off) during the immune response, but the expression was changed relative to the (unparasitized) controls (Wertheim et al, 2005). The continuous expression of all these genes in unparasitized samples implies that the immune response consists at least partially of a modulation of other ongoing developmental and metabolic processes. These expression data provided some evidence that such modulation may incur some costs. A suite of metabolic genes was down-regulated during the immune response, and these genes shared the same over-represented TFBM in the upstream regions as some suites of the upregu-lated 'immunity' genes (Wertheim et al., 2005). The authors proposed that the immune response redirected these transcription factors away from their normal function, at the cost of metabolic processes. In addition, a group of genes involved in puparial adhesion proteins showed a significant reduction in their expression in infected larvae relative to the controls at the very last time point. This likely reflected the known delay in pupation that parasitized flies incur relative to their controls.

Some of the other transcriptomic studies also found indications for costs associated with the immune response. After parasitoid attack, a large group of genes for the generation of energy were upregulated in parasitized larvae, while developmental genes were downregulated (Schlenke et al., 2007). Among the genes that are upregulated after infection with a microsporidium, several had annotations related to carbohydrate metabolism, including the transcription factor Sugarbabe (CG3850), a carbohydrate transporter (CG7801), and a phosphatase involved in trehalose biosynthesis (CG5171) (Roxstrom-Lindquist et al., 2004).

Once activated, the immune response needs to be kept in check to avoid the deleterious effects on fitness. The costs of an activated (or overactive) immune system include reduced fecundity, hyper-sensitivity to infection, cancer, (auto)inflammatory diseases, or developmental defects (Zerofsky et al., 2005; Bischoff et al, 2006; Aggarwal and Silverman, 2008). Multiple negative regulators of the immunity pathways have been identified in Drosophila, including feedback loops, degrading agents of the triggering molecules of the immunity pathways, and possibly a repressosome that binds to the promoter regions of effector genes (reviewed in Aggarwal and Silverman, 2008).

All these costs discussed so far reflect the costs of actual resistance: mobilizing the immune system in the event of an infection. But what about the costs of having the ability to produce a strong immune response? To identify the genes that are involved in a strong immune system, we selected for increased parasitoid resistance in the laboratory, and compared the expression of selected and control flies during their development before they were exposed to parasitoids. Hence, we only measured the changes in expression in flies with increased resistance in anticipation of parasitism, and we validate these genes in replicate control and selection lines to rule out genetic drift. In addition to a number of genes with strong differences in expression between the control and selection line flies, we find evidence for hundreds of genes with small but very consistent changes in expression (Wertheim et al, unpublished work). This suggests that the investment in a stronger immune system is not a simple allelic trait, but results in a significant reorganization of many developmental processes in the growing flies.

Crucially, the Toll and JAK/STAT pathways are not functioning exclusively in the immune response, but are also important for the proper differentiation and morphogenesis of multiple tissues during development (Kambris et al, 2002). Similarly, most of the serine protease molecules are important in both development and immunity (Shah et al., 2008). This dual function of the pathways and molecules supports the notion that an investment in immune responses is likely to harbour side effects in other processes. It also links in to costs of having increased resistance, as identified by the selection experiments discussed above. These showed that increased resistance to parasitoids, mites, and microsporidia all resulted in a lower larval competitive ability, which was tentatively linked to reduced head musculature (Kraaijeveld et al, 2002).

Was this article helpful?

0 0
How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment