From pathogen to a commensal: modification of the interaction during chronic infection by the absence of host insulin signalling.

The nematode worm depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen (CBX102 strain) had a reduced lifespan and vigour. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, the long-lived mutant was resistant to chronic infection, showing reduced colonisation and higher vigour. In fact, UV336 interaction with resulted in a host lifespan extension beyond OP50, the strain used for laboratory culture. Longevity and vigour of mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Our results indicate that the interaction between host genotype and strain-specific bacteria determines longevity and health for .