The enormously large and hence vulnerable surface of the vertebrate gastrointestinal tract is largely protected from pathogenic micro-organisms by a mucous matrix made of water, glycoproteins and antimicrobial substances. The gastrointestinal tract of insects is also exposed to many kinds of potentially harmful micro-organism, some of which are relevant to public health because they can be transmitted to humans through infected insect bites. However, insects do not secrete protective intestinal mucous. Instead, they produce a peritrophic matrix (PM) composed of a chitin mesh and glycoproteins, many of which have a chitin-binding domain to associate with chitin. As the PM lines the midgut epithelium, there was speculation about its potential function as a barrier to infection by pathogens residing in the gut content. Yet there was no clear evidence supporting this assumption until a team of Swiss scientists, led by Bruno Lemaitre, published the first genetic evidence for a protective role of the PM against bacterial infection in PNAS.
In a previous study, Lemaitre and his team examined the immune response in the Drosophila gut and made the exceptional observation that a gene for a putative eye lens protein called Drosocrystallin (Dcy) is strongly up-regulated in the gut of adult flies in response to oral infection with pathogenic bacteria. As this protein contains a chitin-binding domain, they went on to test the possibility that Dcy might be a component of the fly's PM. Indeed, when they looked for Dcy in the insect's gut using anti-Dcy antibodies they found that the protein localizes to the PM. Next, they analysed a Drosophila strain that lacks a functional version of the Dcy protein and found that the insect's life-span was significantly reduced. And when they took a closer look at the mutant's intestine, the scientists observed that the thickness of the PM was significantly reduced and its permeability was increased. Being immunologists, they wondered whether flies lacking the dcy gene would be more susceptible to oral bacterial infections than wild-type flies.
To test this, they fed dietary solutions containing pathogenic bacteria to Drosophila and monitored the flies' mortality at different time points. The mutant flies lacking the fully formed PM were more susceptible to bacterial infection. The scientists also observed increased mortality when they fed solutions of bacterial toxins to the flies, leading them to conclude that the PM detains bacterial toxins – especially pore-forming toxins – to prevent them from damaging intestinal cells.
By analysing mutant flies defective in the dcy gene, Lemaitre and his colleagues have provided the first genetic evidence that the PM plays a pivotal role in defence against enteric bacteria in Drosophila by limiting the effect of bacterial toxins. Certainly, we are in the early stages of discovering the role of the PM in innate immunity; however, Lemaitre's team's discovery will doubtless inspire future studies to reveal the precise function of individual PM proteins in fighting infections caused by bacteria and other micro-organisms. The old idea of the PM as an attractive target for insect control may yet be resurrected in order to develop novel integrated pest management strategies.
