Distinct Members of the C. elegans CeMbio Reference Microbiota Exert Cryptic Virulence that is Masked by Host Defense

Abstract

Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health. Here, we turn to the simple organism C. elegans, a powerful whole- animal model, to study host-microbiota interactions. We show the differential ability of individual C. elegans microbiota members to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct microbiota members differed in their ability to activate the conserved pathways, the ability to activate did not correlate with decreased lifespan in wild type or immunodeficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host’s lifespan if host defense is compromised. The nervous system innervates barrier tissues and regulates the immune response. How neurons detect microbes and subsequently regulate host immune response remains an active area of investigation. We show that cholinergic signaling can regulate HLH-30/TFEB activation. In addition, we find S. aureus infection decreases ASH-mediated avoidance behavior and causes ASH neuronal degeneration. These data support the C. elegans nervous system as a critical microbial sensor and regulator of host defense. These findings can be translated to advance ongoing research of complex intestinal-microbiota and neuronal-microbe interactions in humans, and how individual microbiota members promote or impair host health.