Figure 3. Interaction of the C. elegans innate immunity with stress and longevity pathways.

Germline depleted nematodes and nematodes lacking functional insulin-like growth factor 1 receptor homolog DAF-2 are long-lived and pathogen resistant. The extended life span under these conditions is believed to largely depend on the FOXO transcription factor DAF-16, which mediates induction of anti-stress genes. Interestingly, also pathogen resistance is to some extent DAF-16 dependent. The PMK-1/p38 MAP kinase, whose main role is to mediate conventional innate immune responses, was also shown to contribute to enhanced pathogen resistance during reduced insulin-like signaling and lack of the germline. Of note, PMK-1 and DAF-16 seem to regulate innate immune responses by activating non-overlapping sets of genes. In addition to its immune function, PMK-1 also contributes to longevity by mediating responses to oxidative stress in a manner dependent on the transcription factor SKN-1. The induction of conventional innate immune response is accompanied by protein folding stress in the endoplasmic reticulum and intestinal oxidative stress. Stress management mechanisms such as ER unfolded protein response are essential for the animal’s survival during infection.