Contribution of microbiota to the innate and acquired gut immunity during health and disease

Abstract

The large number of microbials in the intestine that overrides the total human cells by ten folds alludes to significant contribution of the microbiota to human health. This is vivid in enteric and some systemic diseases emanating from disruption of the microbiota. The microbiota influences the development and functioning of both, innate and acquired immune systems for gut health. The effect of microbiota spills throughout the various components of the gut immune systems from “primitive” non specific pattern recognition receptors (PRR) to most specific adaptive T cell responses. To induce immune responses, commensal microbes are recognized by PRRs, which in turn regulate mucosal innate immunity and inflammatory responses. PRRs detect microbe-associated molecular patterns (MAMPs or "infectious non-self") or endogenous "danger signals" derived from stressed, damaged or infected tissue to stimulate the intestinal innate immunity that initiates adaptive immune responses. MAMPs include peptidoglycans, lipoproteins, lipopolysaccharides, teichoic acids, CpG DNA motif, double strand RNA and flagellin. In a balanced microbiota profile, PRR signaling ensures immune homeostasis and protects the host against enteral pathogens. Chapter one of this book will discuss the influence of the microbiota to PRR signaling during health and disease for intestinal immunity. Chapter two of the book focuses on a second level of innate immune system. This involves cells of the innate immune system that are responsible for driving non-specific innate immunity. They include natural killer cells, mast cells, eosinophils, basophils and the phagocytic cells including macrophages, neutrophils and dendritic cells. However, owing to the great commitment of macrophages and dendritic cells, a separate chapter for these two phagocytic cell types is allocated. Thus chapter two discusses the influence of microbiota on innate cells engendering intestinal immunity under health and disease. It concludes the innate immune system of the intestine. Macrophages and dendritic cells are professional antigen presenting cells. They sample antigens from the intestinal lumen, process, and present them to cells of the adaptive immune system. Despite of enormous types of enteral antigens ranging from harmful to beneficial, the antigen presenting cells are capable of efficiently discriminating them and driving respective responses to effector cells of the adaptive immune system. While dendritic cells are capable of priming T cell responses, macrophages do polarize the responses. As to how the microbiota influences the functioning of these cells, chapter three is devoted to discuss that phenomenon. The chapter links innate and adaptive intestinal immune systems since macrophages and dendritic cells lie in the interface between innate and adaptive immune systems. The acquired or adaptive immunity of the gut is split in humoral and cellular components. The humoral immune system is mainly geared by gut-associated lymphoid tissue (GALT) whose components include effector (i.e. epithelial lymphocytes and lamina propria) and inductive (i.e. mesenteric lymph nodes, Peyer’s patches, isolated lymphoid follicles, and cryptopatches) sites. It is interesting to note that microbiota influences GALT development and functioning during health and diseases. In germ free animals and those with disrupted microbita, GALT functioning is heavily compromised leading to diseases. Restoration of normal microbiotal profile to such individuals cures the disorders. Chapter four of this book will describe how the microbiota interacts with GALT and other components of the humoral immune system to maintain intestinal immunity under health and disease. The last chapter, chapter 5, focuses on the second part of the adaptive immune system which is cellular immune system. This system is dominated by several CD4 and CD8 lymphocytes that drive the cellular adaptive immune system. The main components are CD4+ cells which include T helper and regulatory T cells. Other T cells include cytotoxic T, memory, natural killer, and mucosa associated invariant T cells. While T helper cells drive most of the inflammatory responses, regulatory T cells downregulate these responses. As such, they are considered potential therapeutic agents of the future. Current knowledge indicates that the functioning of most, if not all, T cells is influenced by the microbiota. Chapter 5 is therefore devoted to discuss how the microbiota interacts with T cells during health and disease to foster intestinal immunity. In the past few years we have encountered mounting evidence showing that the microbiota plays essential role in regulating and maintaining host’s intestinal immunity. This is done through various ways including; regulation of mucin gene expression by goblet cells, modification of glycosylation of mucus to interfere with bacterial adhesion, colonization and invasion, induction of secretion of antimicrobial peptides by intestinal Paneth cells, regulation of alterations of intestinal permeability caused by infection, stress, and inflammation, and influences on development of mucosal and systemic immunity. It is becoming well comprehended that microbiota is pivotal to the intestinal immunity through crosstalk with the epithelium, immune cells and the immune system in general. Disruption of microbiota balance often leads to disease. This book explores recent findings on how microbiota influences the intestinal immune responses, both innate and adaptive, to foster the intestinal mucosal immunity. The insight gained could contribute to designing approaches suitable for treating gastrointestinal diseases caused by disruption of the microbiota.