The Dbl-1/TGF-β Signaling Pathway Regulates Pathogen-Specific Innate Immune Responses in <i>Caenorhabditis Elegans</i>

Abstract

Generating specific, robust innate immune responses to different bacteria is vital for animal survival. Here, we address the role of transforming growth factor β (TGF- β) DBL-1 in regulating signature host defense responses in Caenorhabditis elegans to human opportunistic Gram-negative and Gram-positive pathogens. Canonical DBL-1 signaling is required to suppress avoidance behavior in response to Gram-negative, but not Gram-positive bacteria. SMA-4/co-Smad acts independently of other DBL-1 core signaling components to suppress avoidance to Gram-positive bacteria, and sma-4 expression is specifically induced in response to Gram-positive bacteria. DBL-1 signaling differentially regulates expression of target innate immunity genes depending on the pathogen. Animals activate DBL-1 pathway activity in response to Gram-negative bacteria and repress it in response to Gram-positive bacteria, demonstrating bacteria-responsive regulation of DBL-1 signaling. These findings highlight a central role for TGF-β and identify a novel role for a co-Smad in tailoring a suite of bacteria-specific host defenses.