Abstract
Host response to pathogens recruits multiple tissues in part through conserved cell signaling pathways. In C. elegans, the bone morphogenetic protein (BMP) like DBL-1 signaling pathway has a role in the response to infection in addition to other roles in development and post-developmental functions. In the regulation of body size and fat storage, the DBL-1 pathway acts through cell autonomous and non-autonomous signaling in the epidermis (hypodermis). We have now elucidated the tissues that respond to DBL-1 signaling upon exposure to bacterial pathogens. The receptors and Smad signal transducers for DBL-1 are expressed in pharyngeal muscle, intestine, and epidermis. We demonstrate that expression of receptor-regulated Smad (R- Smad) gene sma-3 in the pharynx is sufficient to improve the impaired survival phenotype of sma-3 mutants and that expression of sma-3 in the intestine has no effect when exposing worms to bacterial infection of the intestine. We also show that two antimicrobial peptide (AMP) genes – abf-2 and cnc-2 – are regulated by DBL-1 signaling through R-Smad SMA-3 activity in the pharynx. Finally, we show that pharyngeal pumping activity is reduced in sma-3 mutants and that other pharynx-defective mutants also have reduced survival on bacterial pathogens. Our results identify the pharynx as a tissue that responds to BMP signaling to coordinate a systemic response to bacterial pathogens.
Author Summary Animals exposed to infection mount a defense through immune activation. Innate immune responses are regulated by conserved cell signaling pathways. One conserved signaling pathway involved in the C. elegans immune response is the BMP-like DBL-1 pathway. Here we demonstrate that cell non-autonomous signaling through DBL-1 mediator SMA-3 plays a significant role in the response to bacterial intestinal infection. We also identify two antimicrobial peptides regulated by this signaling mechanism in response to bacterial infection. Our work provides insight into the way in which the BMP-like signaling triggers a systemic response to regulate immunity.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We re-analyzed expression of GFP::SMA-3 in our putative epidermal-specific strain, and updated conclusions accordingly.
