Avoidance behavior independent of innate-immune signaling seen in Caenorhabditis elegans challenged with Bacillus...

Small organisms, like the nematode C. elegans, are emerging as insightful models in which to study host/pathogen interactions and the evolving interplay between host defenses and microbial offenses. In C. elegans the innate immune response has been shown to be connected to the DAF-2 insulin/insulin-like growth factor 1 (IGF-1) signal pathway, a critical transduction pathway that mediates stress response in the worms via the DAF-16 FOXO/forkhead transcription factor. Our studies of the C. elegans' phenotypes that are associated with behavioral innate immune response (avoidance behavior) and IGF-1 signaling perturbations (lifespan effects) led us to question the cause of the avoidance behavior observed when C. elegans are challenged with B. anthracis. While worms indeed avoid B. anthracis, and this behavior seems to be partly tied to IGF-1 signaling, the bacteria have neither nematocidal nor visible pathogenic effects on the worms. In fact, worms fed B. anthracis alone exhibit extended lifespans. We demonstrate that the extended lifespan phenotype seen in worms fed B. anthracis is likely the result of calorie restriction, and that worms do not eat B. anthracis even when avoidance behaviors have been suppressed. We further demonstrate a large time lag between the onset of avoidance behavior (which occurs upon contact with B. anthracis), and the induction of IGF-1 signaling (which occurs much later) in worms fed B. anthracis. Taken together, our data demonstrate behavioral avoidance that does not appear to be linked to a measurable immune response. We propose that, in some situations, avoidance behaviors categorized as immunological might be more accurately described as broad foraging behaviors induced in worms presented with a non-preferred food choice, or with a food choice that is either difficult or impossible for the worms to ingest.