Immune-directed support of rich microbial communities in the gut has ancient roots

Abstract

The animal gut serves as a primary location for the complex host-microbe interplay that is essential for homeostasis and may also reflect the types of ancient selective pressures that spawned the emergence of immunity in metazoans. In this review, we present a phylogenetic survey of gut host-microbe interactions and suggest that host defense systems arose not only to protect tissue directly from pathogenic attack but also to actively support growth of specific communities of mutualists. This functional dichotomy resulted in the evolution of immune systems much more tuned for harmonious existence with microbes than previously thought, existing as dynamic but primarily cooperative entities in the present day. We further present the protochordate Ciona intestinalis as a promising model for studying gut host-bacterial dialogue. The taxonomic position, gut physiology and experimental tractability of Ciona offer unique advantages in dissecting host-microbe interplay and can complement studies in other model systems.

Keywords: Ciona intestinalis; Gut biofilms; Gut host–microbe interactions; Gut immune effectors; Gut immune evolution; Mutualism.

Figure 1

Phylogenetic relationships of the taxonomic groups discussed in this review. Relative times of divergence are not to scale. Groupings of particular phyla are indicated by text at right.

Figure 2

(A) Schematic diagram of a generic animal gut ecosystem. Dietary intake and microbes in the lumen (top) flow through the alimentary canal alongside the gut epithelium (middle), with immune and other host cell types occupying the lamina space interior to the gut wall (bottom). Bacteria in the lumen may be transient occupants (blue), commensal/biofilm residents (green), pathogenic invaders (orange) or opportunistic invaders (black). Flow of gut contents is indicated by arrow. (B) Schematic cross section through a Cnidarian polyp showing the simple gastric cavity; oral opening on top. Tissue layers and gut anatomical features are labeled. Flow of food into and out of the oral opening is indicated by arrow. (C) Segmented gut found in most bilaterian animals. Foregut may be a simple tube or elaborated into a stomach (dashed line). (D) Haematoxylin-eosin stained section of Ciona intestinalis stomach. Lu, lumen; E, gut epithelium; La, lamina.

Figure 3

(A) Life cycle of Ciona intestinalis, including from left to right: swimming tadpole larva stage, attached larva, tailbud retraction and onset of metamorphosis, early juvenile (not feeding; unopened siphons) and adult (with siphon flow indicated by arrows). (B) Illustration of high-throughput, parallel experiments using the Ciona system to investigate the response of five parallel populations of idividually attached Ciona to three experimental conditions (standard tissue culture dishes shown). “Populations” are interchangeable with “replicates;” additional replicates allow the production of more genetic material for study. Pooled replicates from different genetic backgrounds can also be performed to strengthen observations.

Figure 4

Biofilm formation mediated by the human immune system. (A) side views of two test tubes (top, bottom) coated with human epithelial cells are shown. In each tube, Escherichia coli bacteria were incubated with nutrient rich media that was replenished on a regular basis. In the top tube, 0.5 mg/ml bovine serum albumin (BSA; a serum protein unrelated to immune function) was added to the media, and in the bottom tube, porcine gastric mucin (50 mg/ml) and human secretory IgA (SIgA; 0.5 mg/ml) were added to the media. Biofilm growth was evident in the tube containing immune-related molecules as shown by increased staining (bottom), but not in the tube without immune related molecules. (B) Schematic diagram demonstrating host-mediated biofilm growth (bottom, attached to epithelium, i.e., immune inclusion), as well as shedding of biofilm fragments (top, unattached to epithelium, i.e., immune exclusion).