Microbiota and mucosal immunity in amphibians

Abstract

We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function. Yet, the literature mainly covers findings obtained in mammals. In this review, we focus on two major themes that emerge from the comparative analysis of mammals and amphibians. These themes concern: (i) the structure and functions of lymphoid organs and immune cells in amphibians, with a focus on the gut mucosal immune system; and (ii) the characteristics of the amphibian microbiota and its influence on mucosal immunity. Lastly, we propose to use Xenopus tadpoles as an alternative small-animal model to improve the fundamental knowledge on immunological functions of gut microbiota.

Keywords: Xenopus; chytrid; microbiome; mucosal immunity; small-animal model.

Figure 1

Orchestration of the mucosal immune system. Based on the environmental signals, DCs secrete cytokines that are critical for the gut immunity. Here are represented the four main CD4⁺ T-cell populations orchestrated by DCs and the cytokines involved in their differentiation, for host defense against danger signals (Th1, Th2, Th17, which are effector T cells) and for the regulation of the homeostasis (Tregs). Once homeostatic control mechanisms are impaired, effector T cells activity can be deleterious. Furthermore, based on their suppression activity against autoreactive T cells, Tregs may favor cancer progression because of the suppression of anti-tumor (autoreactive) T cells.

Figure 2

A comparison of gut microbiome taxonomic profiles in fish, frog, mice, and human. Comparison between four adult vertebrate gut microbiomes. Phylum are represented by colors, and class for the most abundant phylum are represented according to the font size. This figure was adapted from Kostic et al. (121) and from available data on SRA database for H. sapiens (ERR139249) (122), M. musculus (SRR513991) (123), D. rerio (ERR012013) (124), and X. laevis (SRX247015) (57). Data were submitted to the Ribosomal Database Project Classifier tool for taxonomy classification (125). This graph was generated using R (http://cran.r-project.org/bin/).

Figure 3

Microbiota and food antigens regulate the gut immune balance. In normal, non-pathological, conditions tolerogenic DCs promote the differentiation of naive CD4⁺ T cells toward Tregs via the expression of transforming growth factor-β (TGF-β). Thus, TGF-β and Tregs are critical in maintaining self-tolerance and immune homeostasis. In the presence of danger signals (pathogens, dysbiosis, …), activated DCs co-stimulate naive CD4⁺ T cells to differentiate into effector Th17 cells. (GEC, gut epithelial cell)