„The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra“ new Publication by Schröder and Bosch

In their recently published article “The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra”, Professor Thomas Bosch and Katja Schröder present the early-emerging metazoan Hydra as a model for epithelial tissue-based innate immunity in the field of metaorganism research.

In the metaorganism perspective, multicellular organisms are not considered within the limits of individual species, but assumed a “metaorganism” or “holobiont” comprised of the macroscopic host and its microbial colonizers including bacteria, archaea, fungi, and eukaryotic species. Over time these organisms have evolved into a multi-organismic functional unit. Keeping the delicate balance of eliminating invading pathogens, while still tolerating beneficial and mutalistic microbes is a critical step between health and disease of an organism. Thus, all multicellular animals ranging from Hydra to humans developed an effective immune system that is responsible for interfacing with the outside world and to either to fend off pathogens, to maintain beneficial microbes, or at least, to tolerate epithelial colonization.

Epithelial surfaces often are covered by a mucus layer that serves dual function by providing a habtitat for distinct microbial species and at the same time displaying a physicochemical barrier that prevents microbes from penetrating the epithelium and spreading systemically within the tissue. Strikingly, the numerous bacteria colonizing mucosal surfaces of barrier organs such as the intestine usually do not induce pathological inflammatory responses. This controlled lack of inflammation and tolerance of a stable and diverse microbiota is a hallmark of the mucosal immune system and crucial for maintaining gut homeostasis. Driven by the emerging awareness that several human diseases are not resuling from invasion by a single pathogen but rather from a shift in the composition of the mutli-species microbial communities, host-microbe interactions have become a rapidly advancing research field over the last two decades. E.g. several studies demonstrated that malfunctioning of specific interactions between the mucosal immune system and the microbiota plays an important role in the etiology of inflammatory bowel diseases (IBD). However, the fundamental principles dictating how environmental factors and host genetic factors combine to shape the complex microbiota in the vertebrate gut are largely unknown and require systematic study.

In the past mucosal immunity has been extensively studied in different vertebrate model organisms. However, mucosal surfaces appeared for the first time about 560 million years ago in early-emerging metazoans, such as the Cnidarian Hydra. Despite the simple body plan consisting of two cell layers and absence of an adaptive immune system, Hydra employs an elaborate innate immune system with cellular and humoral pathways to detect and interact with microbes. Previous systematic analysis of the Hydra microbiome has shown that these animals harbour multi-species bacterial communities on top of their epithelium in a mucus-like layer, named glycocalyx. Similar to the mammalian gut, Hydra’s glycocalyx has two functionally distinct compartments: an outer mucus-like layer that forms the habitat for the microbiota and an inner stratified layer that is devoid of bacteria and acts as a physicochemical barrier. Since the genome and the epithelial organization are remarkably similar to those of vertebrate mucosal surfaces, these animals offer unique insights into innate immune responses of epithelial barriers. The bacterial diversity of Hydra’s microbiota appears to be far lower than in the vertebrate gut. However, its assembly process after birth displays important parallels to vertebrates. Furthermore, Hydra’s microbiota was shown to effectively inhibit colonization and overgrowth of a fungal pathogen – a phenomenon well known as colonization resistance from vertebrate gut. Simple animal models possessing mucosal epithelia colonized with a specific microbiota of manageable diversity therefore may allow us to untangle how microbial communities interact as a spatially and temporally dynamic network on host mucosal surfaces.

Original publication:
Schröder K, Bosch, T C G (2016); The Origin of Mucosal Immunity: Lessons from the Holobiont Hydra. mBio, 7(6): e01184-16. doi: https://doi.org/10.1128/mBio.01184-16