Glia of C. elegans coordinate the heat shock response independent of the neuronal thermosensory circuit and serotonin
As organisms age, they lose the ability to induce appropriate stress responses, becoming vulnerable to protein toxicity and tissue damage. Neurons can signal to peripheral tissues to induce protective organelle-specific stress responses. Recent work has demonstrated a novel and independent role of glia in inducing such responses. Here, we show that overexpression of heat shock factor 1 (hsf-1) in the four astrocyte-like cephalic sheath cells of C. elegans is sufficient to induce a non-cell autonomous cytosolic unfolded protein response (UPR), also known as the heat shock response (HSR), in distal cells. These animals upregulate the HSR in peripheral cells and have increased lifespan and resistance to heat stress. This glial HSR regulation is independent of the canonical neuronal thermosensory circuit and of known neurotransmitters but is dependent on the small clear vesicle release protein UNC-13. Additionally, HSF-1 and the FOXO transcription factor DAF-16 are partially required in peripheral tissues for increase of non-autonomous HSR, lifespan, and thermotolerance. We find that cephalic sheath glial hsf-1 over-expression leads to increased pathogen resistance, which suggests a role for this signaling pathway in immune function.