NALT M cells are important for immune induction for the common mucosal immune system.

Nasopharynx-associated lymphoid tissue (NALT) is one of the major constituents of the mucosa-associated lymphoid tissue (MALT), and has the ability to induce antigen-specific immune responses. However, the molecular mechanisms responsible for antigen uptake from the nasal cavity into the NALT remain largely unknown. Immunohistochemical analysis showed that CCL9 and CCL20 were co-localized with glycoprotein 2 (GP2) in the epithelium covering NALT, suggesting the existence of M cells in NALT. In analogy with the reduced number of Peyer's patch M cells in CCR6-deficient mice, the number of NALT M cells was drastically decreased in CCR6-deficient mice compared with the wild-type mice. Translocation of nasally administered Salmonella enterica serovar Typhimurium into NALT via NALT M cells was impaired in CCR6-deficient mice, whereas S. Typhimurium demonstrated consistent co-localization with NALT M cells in wild-type mice. When wild-type mice were nasally administered with an attenuated vaccine strain of S. Typhimurium, the mice were protected from a subsequent challenge with wild-type S. Typhimurium. Antigen-specific fecal and nasal IgA was detected after nasal immunization with the attenuated vaccine strain of S. Typhimurium only in wild-type mice but not in CCR6-deficient mice. Taken together, these observations demonstrate that NALT M cells are important as a first line of defense against infection by enabling activation of the common mucosal immune system (CMIS).

Application of Market Basket Analysis for the Visualization of Transaction Data Based on Human Lifestyle and Spectroscopic Measurements.

With the innovation of high-throughput metabolic profiling methods such as nuclear magnetic resonance (NMR), data mining techniques that can reveal valuable information from substantial data sets are constantly desired in this field. In particular, for the analytical assessment of various human lifestyles, advanced computational methods are ultimately needed. In this study, we applied market basket analysis, which is generally applied in social sciences such as marketing, and used transaction data derived from dietary intake information and urinary chemical data generated using NMR and inductively coupled plasma optical emission spectrometry measurements. The analysis revealed several relationships, such as fish diets with high trimethylamine N-oxide excretion and N-methylnicotinamide excreted at higher levels in the morning and produced from a protein that was consumed one day prior. Therefore, market basket analysis can be applied to metabolic profiling to effectively understand the relationships between metabolites and lifestyle.

Comparative analysis of chemical and microbial profiles in estuarine sediments sampled from Kanto and Tohoku regions in Japan.

Estuarine environments accumulate large quantities of organic matter from land masses adjoining the sea, and this is consumed as part of the detritus cycle. These environments are rich in biodiversity, and their ecosystem services greatly benefit humans. However, the estuarine environments have complicated aqueous ecosystems, thus the comprehensive evaluation of biotic interactions and stability is difficult using conventional hypothesis-driven approaches. In this study, we describe the advancement of an evaluation strategy for characterizing and visualizing the interactions and relationships among the microorganisms and chemicals in sediment ecosystems of estuarine environments by a combination of organic matter and elemental profiling as well as microbial profiling. We also report our findings from a comparative analysis of estuarine and coastal environmental samples collected from the Kanto and Tsunami-affected Tohoku regions in Japan. The microbial-gated correlation deployed from the coefficient of microbiota from the correlation matrix and network analysis was able to visualize and summarize the different relationships among the microbial communities, sediment organic matter, and element profiles based on geographical differences in Kanto and Tohoku regions. We demonstrated remarkable estuarine eutrophication in the Kanto region based on abundant sediment polypeptide signals and water nitrogen ions catabolized by microbiota. Therefore, we propose that this data-driven approach is a powerful method for analyzing, visualizing, and evaluating complex metabolic dynamics and networks in sediment microbial ecosystems and can be applied to other environmental ecosystems, such as deep sea sediments and agronomic and forest soils.

Solid-, solution-, and gas-state NMR monitoring of ¹³C-cellulose degradation in an anaerobic microbial ecosystem.

Anaerobic digestion of biomacromolecules in various microbial ecosystems is influenced by the variations in types, qualities, and quantities of chemical components. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for characterizing the degradation of solids to gases in anaerobic digestion processes. Here we describe a characterization strategy using NMR spectroscopy for targeting the input solid insoluble biomass, catabolized soluble metabolites, and produced gases. ¹³C-labeled cellulose produced by Gluconacetobacter xylinus was added as a substrate to stirred tank reactors and gradually degraded for 120 h. The time-course variations in structural heterogeneity of cellulose catabolism were determined using solid-state NMR, and soluble metabolites produced by cellulose degradation were monitored using solution-state NMR. In particular, cooperative changes between the solid NMR signal and ¹³C-¹³C/¹³C-¹²C isotopomers in the microbial degradation of ¹³C-cellulose were revealed by a correlation heat map. The triple phase NMR measurements demonstrated that cellulose was anaerobically degraded, fermented, and converted to methane gas from organic acids such as acetic acid and butyric acid.

The epithelia-specific membrane trafficking factor AP-1B controls gut immune homeostasis in mice.

BACKGROUND & AIMS: Epithelial cells that cover the intestinal mucosal surface maintain immune homeostasis and tolerance in the gastrointestinal tract. However, little is known about the molecular mechanisms that regulate epithelial immune functions. Epithelial cells are distinct in that they are highly polarized; this polarity is, at least in part, established by the epithelium-specific polarized sorting factor adaptor protein (AP)-1B. We investigated the role of AP-1B-mediated protein sorting in the maintenance of gastrointestinal immune homeostasis. METHODS: The role of AP-1B in intestinal immunity was examined in AP-1B-deficient mice (Ap1m2(-/-)) by monitoring their phenotypes, intestinal morphology, and epithelial barrier functions. AP-1B-mediated protein sorting was examined in polarized epithelial cells from AP-1B knockdown and Ap1m2(-/-) mice. RESULTS: Ap1m2(-/-) mice developed spontaneous chronic colitis, characterized by accumulation of interleukin-17A-producing, T-helper 17 cells. Deficiency of AP-1B caused epithelial immune dysfunction, such as reduced expression of antimicrobial proteins and impaired secretion of immunoglobulin A. These defects promoted intestinal dysbiosis and increased bacterial translocation within the mucosa. Importantly, AP-1B deficiency led to mistargeting of a subset of basolateral cytokine receptors to the apical plasma membrane in a polarized epithelial cell line and in colonic epithelial cells from mice. AP1M2 expression was reduced significantly in colonic epithelium samples from patients with Crohn's disease. CONCLUSIONS: AP-1B is required for proper localization of a subset of cytokine receptors in polarized epithelial cells, which allows them to respond to cytokine signals from underlying lamina propria cells. The AP-1B-mediated protein sorting machinery is required for maintenance of immune homeostasis and prevention of excessive inflammation.

Psg18 is specifically expressed in follicle-associated epithelium.

Pregnancy-specific glycoproteins (Psgs) secreted by the placenta regulate the immune system to ensure the survival of the fetal allograft by inducing IL-10, an anti-inflammatory cytokine. However, it is unknown whether Psgs are involved in more general aspects of immune response other than maternal immunity. Here, we report that Psg18 is highly expressed in the follicle-associated epithelium (FAE) overlaying Peyer's patches (PPs). Bioinformatics analysis with Reference Database for Immune Cells (RefDIC) as well as RT-PCR data demonstrated that Psg18 is exclusively expressed in FAE in adult mice, in contrast to other Psg family members that are either not expressed or only slightly expressed in FAE. Psg18 expression was observed in FAE of germ-free-conditioned mice, and was slightly upregulated after bacterial inoculation. In situ hybridization analysis revealed that Psg18 is widely expressed throughout FAE. Furthermore, Psg18 protein is deposited on the extracellular matrix in the subepithelial dome beneath FAE, where antigen-presenting cells accumulate. These results suggest that Psg18 is an FAE-specific marker protein that could promote interplay between FAE and immune cells in mucosa-associated lymphoid tissues.