BMP signaling in theC. elegansimmune response to bacterial pathogen regulates anti-microbial peptide expression through cell non-autonomous activity

AbstractHost response to pathogens recruits multiple tissues in part through conserved cell signaling pathways. InC. 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 as well as several post-developmental functions. In the regulation of body size and fat storage, the DBL-1 pathway has been shown to act through cell autonomous and non-autonomous signaling in the epidermis (hypodermis). We have now elucidated the tissues that respond to DBL-1 signaling in the response to bacterial pathogens. The receptors and Smad signal transducers for DBL-1 are expressed in the pharynx, intestine, and epidermis. We demonstrate that expression of receptor-regulated Smad (R-Smad) genesma-3in either the epidermis or pharynx is sufficient to improve the impaired survival phenotype ofsma-3mutants and that expression ofsma-3in the intestine has no effect when exposing worms to bacterial infection of the intestine. We also show by qRT-PCR that two antimicrobial peptide (AMP) genes –abf-2andcnc-2– are regulated by DBL-1 signaling through R-Smad SMA-3. We show that this AMP regulation is similarly cell non-autonomous, as expression ofsma-3in either the epidermis or the pharynx is sufficient to induce bothabf-2andcnc-2expression in animals exposed to bacterial infection. These results demonstrate that in response to bacterial pathogen, the DBL-1 pathway regulates AMP expression through R-Smad SMA-3 in a cell non-autonomous manner to confer immunity against infection.Author SummaryAnimals exposed to infection mount a defense through immune activation. Innate immune responses are regulated by conserved cell signaling. One conserved signaling pathway involved in theC. elegansimmune 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.