Exploring Foundations of Animal Host-microbe Interactions in a Freshwater Sponge

Abstract

The most ancient eukaryotic immune defense mechanisms evolved in unicellular species. Multicellular eukaryotes, however, expanded these mechanisms to meet challenges unique to multicellular life, including barrier formation, long-distance cell signaling, and coordinated responses that eliminate microbial threats while minimizing damage to the host. As such, animal immune signaling pathways are exceptionally intricate and diverse. Though, most of what is understood about animal host–microbe interactions stems from a small handful of model systems. Here, I evaluate host–microbe interactions and innate immunity in sponges using the highly tractable freshwater sponge, Ephydatia muelleri. I report the discovery of an external host-derived matrix that physically separates host cells from environmental microbes, which reconciles longstanding inconsistencies between bulk-sequencing and ultrastructural surveys. I additionally take a reductionist approach in evaluating the E. muelleri response to immunogenic MAMPs (e.g., LPS), and show that these responses frequently converge on the ancient, highly conserved NF-κB transcriptional complex—a signaling hub that directly initiates inflammation in other animals. I further probe the innate immune responses of E. muelleri by developing a tractable infection model with the opportunistic pathogen, Legionella pneumophila. I show that L. pneumophila employs similar infection mechanisms in E. muelleri as for other eukaryotic hosts, including humans. This work highlights the importance of studying non-model animal immune systems to inform ancestral states and identify fundamental aspects of animal host–microbe interactions.