Abstract
The gut microbiota is essential for the development and regulation of the immune system and the metabolism of the host. Germ-free animals have altered immunity with increased susceptibility to immunologic diseases and show metabolic alterations. Here, we focus on two of the major immune-mediated microbiota-influenced components that signal far beyond their local environment. First, the activation or suppression of the toll-like receptors (TLRs) by microbial signals can dictate the tone of the immune response, and they are implicated in regulation of the energy homeostasis. Second, we discuss the intestinal mucosal surface is an immunologic component that protects the host from pathogenic invasion, is tightly regulated with regard to its permeability and can influence the systemic energy balance. The short chain fatty acids are a group of molecules that can both modulate the intestinal barrier and escape the gut to influence systemic health. As modulators of the immune response, the microbiota-derived signals influence functions of distant organs and can change susceptibility to metabolic diseases.
Highlights
The activation or suppression of the toll-like receptors (TLRs) by microbial signals can dictate the tone of the immune response, and they are implicated in regulation of the energy homeostasis
The absence of gut microbiota leads to functional alterations in immune and intestinal epithelial cells, which express less microbe sensing toll-like receptors (TLR) [19] and major histocompatibility complex II molecules for antigen presentation [20]
There are 10 TLRs in humans and 12 in mice found on the cell or endosomal membranes of different cell types including macrophages, dendritic cells (DCs), and nonimmune cells such as epithelial cells, hepatocytes, or adipocytes
Summary
The human microbiota comprises an enormous amount and variety of microorganisms. Among archea, eukarya, and viruses, bacteria are the most abundant inhabitants of the human host. There are 10 TLRs in humans and 12 in mice found on the cell or endosomal membranes of different cell types including macrophages, dendritic cells (DCs), and nonimmune cells such as epithelial cells, hepatocytes, or adipocytes Activation of such receptors initiates downstream signaling cascades that often result in induction of cytokine expression. One ligand of TLR2 is polysaccharide A (PSA) from Bacteroides fragilis that induces anti-inflammatory responses, activates plasmacytoid DCs, interleukin 10 (IL-10) production of CD4+ T cells, promotes clonal expansion and induction of Treg cells, and suppresses Th17 production in the gut (Figure 1) [29,30,31] These aspects potentially contribute to the amelioration of inflammation in animal models such as experimental autoimmune encephalomyelitis and colitis after PSA administration [29, 32, 33] or after colonization of GF mice with Bacteroidetes [34].
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