Intestinal M cells Ohno, Hiroshi
Journal of biochemistry (Tokyo),
02/2016, Letnik:
159, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal ...epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer's patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions.
Abstract
Abstract
The gut microbiota strongly impacts the physiology and pathology in the host. To understand the complex interactions between host and gut microbiota, an ‘integrated omics’ approach ...has been employed, where exhaustive analyses for the different layers of cellular functions, such as epigenomics, transcriptomics and metabolomics, in addition to metagenomics, are combined. With this approach, the mechanisms whereby short-chain fatty acids (SCFAs) regulate host defense and the immune system have been elucidated. In a gnotobiotic mouse model of enterohemorrhagic Escherichia coli infection, Bifidobacterium-derived acetate can protect from infection-mediated death by changing the gene expression profile of colonic epithelial cells. It has also been shown that gut microbiota-derived butyrate enhances colonic regulatory T-cell differentiation through its epigenetic modulatory ability via histone deacetylase inhibition. SCFAs are involved in many other immunomodulatory effects as well as host pathophysiological conditions. Dysbiosis in the gut has been implicated in the pathogenesis of many diseases. Although the causal relationship of gut microbial dysbiosis and/or metabolites with pathogenesis is mostly unknown, mechanistic insights have been elucidated in some cases. Metabolism in the gut microbiota and host liver produces trimethylamine N-oxide, which is known to aggravate atherosclerosis, and a secondary bile acid deoxycholate, which reportedly induces non-alcoholic steatohepatitis-related hepatocellular carcinoma. It has been reported that secondary bile acids could also induce the differentiation of peripherally derived regulatory T cells in the gut. Further studies on the interactions between the host and gut microbiota could lead to the development of new therapeutic strategies as well as in preventive medicine.
Integrated omics reveals how microbial metabolites regulate immunity
Abstract
The mammalian intestine is home to trillions of microbes, and their colonization contributes to host physiology through the production of indispensable metabolites and competition against ...pathogens. However, it is also important to balance this symbiotic relationship, as overgrowth and translocation of microbes could trigger a fatal infection. IgA is the major immunoglobulin class produced and secreted in the intestine and is considered to play a pivotal role in maintaining homeostasis. In this review, we summarize recent studies exploring the interactions between IgA and the gut microbiota and explain how different types of IgA could coexist to regulate the gut microbiota. In particular, we discuss two important aspects of IgA in controlling the gut microbes: function and specificity. Differences in these two aspects appear attributable to how IgA is induced and are associated with the functions of IgA as well. Together, our review delineates a recent understanding of IgA–microbiome interactions and proposes a future direction to clarify its complexity.
The prevalence of autoimmune diseases (ADs) worldwide has rapidly increased over the past few decades. Thus, in addition to the classical risk factors for ADs, such as genetic polymorphisms, ...infections and smoking, environmental triggers have been considered. Recent sequencing-based approaches have revealed that patients with extra-intestinal ADs, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. Faecal microbiota transplantation or inoculation with specific microbes in animal models of ADs support the hypothesis that alterations of gut microbiota influence autoimmune responses and disease outcome. Here, we describe the compositional and functional changes in the gut microbiota in patients with extra-intestinal AD and discuss how the gut microbiota affects immunity. Moreover, we examine how the gut microbiota might be modulated in patients with ADs as a potential preventive or therapeutic approach.
Snowfall is regarded as a carrier of airborne microplastics (MPs). Deposited snow can function as a temporary reservoir for atmospheric MPs. Nevertheless, knowledge and understanding of MPs in snow ...remain sparse. This study investigates the abundance, composition, size (> 30 µm), and shape of MPs in snow specimens from various nature preservation areas and also from urban sites in Hokkaido. Various polymeric-type MPs with mostly fragmentary shapes were detected among the specimens. More than half of MPs were in the smallest size class (30-60 µm), implying the presence of more MPs below the limit (< 30 µm). Concentrations of MPs ranged from 1.5 × 10
to 4.2 × 10
particles/L. The results demonstrated that microplastic abundance generally decreases concomitantly with increasing remoteness of sampling sites. Observed features of MPs at different locations and their relation to geographical settings have indicated that the ubiquitously observed fine particles (mainly alkyd, ethylene-vinyl acetate, and polyethylene) are attributable to long-distance atmospheric transportation, whereas the rubber and larger particles especially found near highways and cities are from local sources of plastic. Taken together, these findings suggest important implications for elucidating the nature and distribution of atmospheric MPs.
The stomach has been thought to host few commensal bacteria because of the existence of barriers, such as gastric acid. However, recent culture-independent, sequencing-based microbial analysis has ...shown that the stomach also harbors a wide diversity of microbiota. Although the stomach immune system, especially innate lymphoid cells (ILCs), has not been well elucidated, recent studies have shown that group 2 ILCs (ILC2s) are the dominant subtype in the stomach of both humans and mice. Stomach ILC2s are unique in that their existence is dependent on stomach microbiota, in sharp contrast to the lack of an impact of commensal microbiota on ILC2s in other tissues. The microbiota dependency of stomach ILC2s is partly explained by their responsiveness to interleukin (IL)-7. Stomach ILC2s express significantly higher IL-7 receptor protein levels on their surface and proliferate more in response to IL-7 stimulation in vitro than small intestinal ILC2s. Consistently, the stomach expresses much higher IL-7 protein levels than the small intestine. IL-5 secreted from stomach ILC2s promotes immunoglobulin (Ig) A production by plasma B cells. In a murine model, stomach ILC2s are important in containing Helicobacter pylori infection, especially in the early phase of infection, by promoting IgA production.
Gut microbiota has extensive and tremendous impacts on human physiology and pathology. The regulation of microbiota is therefore a cardinal problem for the mutualistic relationship, as both microbial ...overgrowth and excessive immune reactions toward them could potentially be detrimental to host homeostasis. Growing evidence suggests that IgA, the most dominant secretory immunoglobulin in the intestine, regulates the colonization of commensal microbiota, and consequently, the microbiota-mediated intestinal and extra-intestinal diseases. In this review, we discuss the interactions between IgA and gut microbiota particularly relevant to human pathophysiology. We review current knowledge about how IgA regulates gut microbiota in humans and about the molecular mechanisms behind this interaction. We further discuss the potential role of IgA in regulating human diseases by extrapolating experimental findings, suggesting that IgA can be a future therapeutic strategy that functionally modulates gut microbiota.
Mast cells are important for eradication of intestinal nematodes; however, their precise mechanisms of action have remained elusive, especially in the early phase of infection. We found that ...Spi-B-deficient mice had increased numbers of mast cells and rapidly expelled the Heligmosomoides polygyrus (Hp) nematode. This was accompanied by induction of interleukin-13 (IL-13)-producing group 2 innate lymphoid cells (ILC2) and goblet cell hyperplasia. Immediately after Hp infection, mast cells were rapidly activated to produce IL-33 in response to ATP released from apoptotic intestinal epithelial cells. In vivo inhibition of the P2X7 ATP receptor rendered the Spi-B-deficient mice susceptible to Hp, concomitant with elimination of mast cell activation and IL-13-producing ILC2 induction. These results uncover a previously unknown role for mast cells in innate immunity in that activation of mast cells by ATP orchestrates the development of a protective type 2 immune response, in part by producing IL-33, which contributes to ILC2 activation.
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•Spi-B-deficient mice are resistant to intestinal helminth infection•Myeloid differentiation is regulated by the Ets transcription factor Spi-B•Mast cells are a potent source of IL-33 and can activate ILC2•The production of IL-33 by mast cells requires their activation through ATP-P2X7
Mast cells are supposed to contribute to protection against helminthic infection in the later phase. Shimokawa and colleagues demonstrate that mast cells play a critical role for activation of ILC2 responsible for parasite expulsion in the early phase.
Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have ...previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease.
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