A Basal Chordate Model for Studies of Gut Microbial Immune Interactions

Abstract

Complex symbiotic interactions at the surface of host epithelia govern most encounters between host and microbe. The epithelium of the gut is a physiologically ancient structure that is comprised of a single layer of cells and is thought to possess fully developed immunological capabilities. Ciona intestinalis (sea squirt), which is a descendant of the last common ancestor of all vertebrates, is a potentially valuable model for studying barrier defenses and gut microbial immune interactions. A variety of innate immunological phenomena have been well characterized in Ciona, of which many are active in the gut tissues. Interactions with gut microbiota likely involve surface epithelium, secreted immune molecules including variable region-containing chitin-binding proteins, and hemocytes from a densely populated laminar tissue space. The microbial composition of representative gut luminal contents has been characterized by molecular screening and a potentially relevant, reproducible, dysbiosis can be induced via starvation. The dialog between host and microbe in the gut can be investigated in Ciona against the background of a competent innate immune system and in the absence of the integral elements and processes that are characteristic of vertebrate adaptive immunity.

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

“…1) and as such lack classical adaptive immunity; nevertheless, they retain and share key, chordate-specific, developmental features that include a notochord, hollow dorsal nerve cord, pharyngeal slits, endostyle and post-anal tail (Brown et al, 2008; Cameron et al, 2000; Cañestro et al, 2003b; Katz, 1983; Kubo et al, 2009; Meinertzhagen and Okamura, 2001; Paris and Laudet, 2008; Shi et al, 2005; Swalla et al, 2000; Swalla and Smith, 2008). Ciona intestinalis , a tunicate with a compartmentalized gut (Burighel and Cloney, 1997; Hirano and Nishida, 2000; Nakazawa et al, 2013) that undergoes epithelial turnover and renewal (Ermak, 1981), is being adapted by our laboratory as a model to help define the evolution of bacterial-immune dialogue in the chordate gut (Dishaw et al, 2012a; Dishaw et al, 2011). Ciona is a suspension (filter) feeder that siphons water continuously, a process that results in the exposure to and consumption of ample amounts of dietary microorganisms.…”

“…Mariculture of Ciona is well established; animals can be grown under microbe-free conditions by the hundreds on standard tissue culture dishes that facilitate the production of large clonal replicates (Fig. 3) (Dishaw et al, 2012a). Current efforts are focused on characterizing the biology of the compartmentalized gut in Ciona and in determining the roles of VCBPs in modulating the composition of bacteria in the gut and facilitating homeostasis.…”

“…Ciona intestinalis has been shown previously to be a relevant model system for studies of development (Baghdiguian et al, 2007; Cañestro et al, 2003; Davidson, 2007; Katz, 1983; Meinertzhagen and Okamura, 2001; Sasakura et al, 2009; Shi et al, 2005) and immune defense (Fujita et al, 2004; Parrinello et al, 2008; Sasaki et al, 2009; Zucchetti et al, 2009) and presently is being developed for studies of gut host-bacterial interactions (Dishaw et al, 2012a; Dishaw et al, 2011). By permitting the experimental dissection of the conversation between host and microbiota at the onset of colonization, the Ciona model promises to reveal chordate rules that govern the biology of colonization.…”

The Ciona intestinalis immune-related galectin genes (CiLgals-a and CiLgals-b) are expressed by the gastric epithelium

“…All in all, the observed differences between CiLgals-a and CiLgals-b mRNAs and proteins localization in the tissue, as well as the differences in the cell features in several histological sections [27], could be mainly imputed to mRNA transcription and protein production phases, and their turnover levels along the tissue as well as to differences between sampled individuals. In this respect, we could speculate that "gland cells" of the gastric epithelium and the furrow tissue rich in vesicles may represent two subsequent phases of the epithelium activity that includes seromucous production [27].…”

“…In this respect, we could speculate that "gland cells" of the gastric epithelium and the furrow tissue rich in vesicles may represent two subsequent phases of the epithelium activity that includes seromucous production [27].…”