BMP signaling to pharyngeal muscle in the C. elegans response to a bacterial pathogen regulates anti-microbial peptide expression and pharyngeal pumping

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, the DBL-1 pathway acts through cell autonomous signal activation in the epidermis (hypodermis). We have now elucidated the tissues that respond to DBL-1 signaling upon exposure to two 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 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 a bacterial pathogen. Our results identify the pharynx as a tissue that responds to BMP signaling to coordinate a systemic response to bacterial pathogens. Significance StatementO_LIInnate immunity is the first line of defense against pathogens. Conserved cell signaling pathways are known to be involved in host-pathogen response, but how they coordinate a systemic response is less well understood. C_LIO_LIIn the nematode C. elegans, bone morphogenetic protein (BMP) signaling is required for survival on pathogenic bacteria. Using transgenic strains, the authors identify a major role for a specific organ, the pharynx, in BMP-dependent survival. C_LIO_LIThese findings demonstrate that an organ can serve as a pathogen sensor to trigger multiple modes of response to bacterial pathogens, include a barrier response and regulation of anti-microbial peptide expression. C_LI