The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra

Abstract

Historically, mucosal immunity—i.e., the portion of the immune system that protects an organism’s various mucous membranes from invasion by potentially pathogenic microbes—has been studied in single-cell epithelia in the gastrointestinal and upper respiratory tracts of vertebrates. Phylogenetically, mucosal surfaces appeared for the first time about 560 million years ago in members of the phylum Cnidaria. There are remarkable similarities and shared functions of mucosal immunity in vertebrates and innate immunity in cnidarians, such as Hydra species. Here, we propose a common origin for both systems and review observations that indicate that the ultimately simple holobiont Hydra provides both a new perspective on the relationship between bacteria and animal cells and a new prism for viewing the emergence and evolution of epithelial tissue-based innate immunity. In addition, recent breakthroughs in our understanding of immune responses in Hydra polyps reared under defined short-term gnotobiotic conditions open up the potential of Hydra as an animal research model for the study of common mucosal disorders.

Compartmentalized Antimicrobial Defenses in Response to Flagellin

“…Given the nature of the mucosa and its continuous exposure to antigens and pathogens, the epithelial cells, that constitute the mucosa, are more than physical barriers between the internal and external environment. The genome of primitive metazoan hydra that emerged more than 500 million years ago, encodes, instead of the typical TLRs, four transmembrane proteins: two proteins constituted by TIR domains and short extracellular regions (HyTRR1 and HyTRR2), and two proteins with LRR-containing ectodomains and short cytoplasmic tails (HyLRR1 and HyLRR2) [87].…”

Rethinking the Role of the Nervous System: Lessons From the Hydra Holobiont

“…[27,28] Until very recently, the epithelial cells of Hydra were considered as prime regulators of the microbiome. [26,29,30] In fact, ectodermal and endodermal cells were shown to express components of signaling pathways for bacterial recognition, such as Toll-like receptor (TLR) mediated MyD88 pathway and NOD-like receptor (NLR) dependent cascade, and to produce a rich cocktail of antimicrobial peptides (AMPs). [29,[31][32][33] As expected, reduced expression of the MyD88 protein in epithelial cells compromised the resistance of Hydra polyps to the pathogenic bacterium Pseudomonas aeruginosa.…”

Competing forces maintain the Hydra metaorganism

“…In the absence of an adaptive immune system, Hydra employs an elaborate innate immune system to detect and interact with microbes using their two cell layers as efficient defense barriers . Invading microorganisms first have to overcome the physicochemical barrier represented by the multilayered glycocalyx that covers the ectodermal epithelium . Complex cellular and humoral pathways represent the second arm of Hydra's immunity .…”

“…Living associated with Hydra , embedded into the mucus‐like layer of Hydra's glycocalyx could be another so far neglected mode of protection of bacteria against phage infections. An accumulation of virus‐like particles (VLPs) at the surface of mucus layers have been reported for different organisms and it has been shown that phages bind to mucus glycoproteins via Ig‐like proteins domains on phage capsids .…”