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https://www.readbyqxmd.com/read/28529928/the-probiotic-compound-vsl-3-modulates-mucosal-peripheral-and-systemic-immunity-following-murine-broad-spectrum-antibiotic-treatment
#1
Ira Ekmekciu, Eliane von Klitzing, Ulrike Fiebiger, Christian Neumann, Petra Bacher, Alexander Scheffold, Stefan Bereswill, Markus M Heimesaat
There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28505210/whole-exome-sequencing-of-a-consanguineous-family-identifies-the-possible-modifying-effect-of-a-globally-rare-ak5-allelic-variant-in-celiac-disease-development-among-saudi-patients
#2
Jumana Yousuf Al-Aama, Noor Ahmad Shaik, Babajan Banaganapalli, Mohammed A Salama, Omran Rashidi, Ahmed N Sahly, Mohammed O Mohsen, Harbi A Shawoosh, Hebah Ahmad Shalabi, Mohammad Al Edreesi, Sameer E Alharthi, Jun Wang, Ramu Elango, Omar I Saadah
Celiac disease (CD), a multi-factorial auto-inflammatory disease of the small intestine, is known to occur in both sporadic and familial forms. Together HLA and Non-HLA genes can explain up to 50% of CD's heritability. In order to discover the missing heritability due to rare variants, we have exome sequenced a consanguineous Saudi family presenting CD in an autosomal recessive (AR) pattern. We have identified a rare homozygous insertion c.1683_1684insATT, in the conserved coding region of AK5 gene that showed classical AR model segregation in this family...
2017: PloS One
https://www.readbyqxmd.com/read/28469619/immune-responses-to-broad-spectrum-antibiotic-treatment-and-fecal-microbiota-transplantation-in-mice
#3
Ira Ekmekciu, Eliane von Klitzing, Ulrike Fiebiger, Ulrike Escher, Christian Neumann, Petra Bacher, Alexander Scheffold, Anja A Kühl, Stefan Bereswill, Markus M Heimesaat
Compelling evidence demonstrates the pivotal role of the commensal intestinal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. Aim of this study was to investigate the impact of antibiotics induced depletion and subsequent restoration of the intestinal microbiota composition on the murine mucosal and systemic immunity. To address this, conventional C57BL/6j mice were subjected to broad-spectrum antibiotic treatment for 8 weeks. Restoration of the intestinal microbiota by peroral fecal microbiota transplantation (FMT) led to reestablishment of small intestinal CD4(+), CD8(+), and B220(+) as well as of colonic CD4(+) cell numbers as early as 7 days post-FMT...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#4
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28424283/simian-immunodeficiency-virus-targeting-of-cxcr3-cd4-t-cells-in-secondary-lymphoid-organs-is-associated-with-robust-cxcl10-expression-in-monocyte-macrophage-subsets
#5
Masayuki Fujino, Hirotaka Sato, Tomotaka Okamura, Akihiko Uda, Satoshi Takeda, Nursarat Ahmed, Shigeyuki Shichino, Teiichiro Shiino, Yohei Saito, Satoru Watanabe, Chie Sugimoto, Marcelo Kuroda, Manabu Ato, Yoshiyuki Nagai, Shuji Izumo, Kouji Matsushima, Masaaki Miyazawa, Aftab A Ansari, Francois Villinger, Kazuyasu Mori
Glycosylation of Env defines pathogenic properties of SIV. We previously demonstrated that pathogenic SIVmac239 and live-attenuated, quintuple deglycosylated Env mutant (Δ5G) target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012). Herein, we studied the host responses relevant to SIV targeting of CXCR3(+)CCR5(+) CD4(+) T cells in SLOs...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28408924/investigation-of-small-bowel-abnormalities-in-hiv-infected-patients-using-capsule-endoscopy
#6
Eiji Sakai, Takuma Higurashi, Hidenori Ohkubo, Kuhihiro Hosono, Atsuhisa Ueda, Nobuyuki Matsuhashi, Atsushi Nakajima
HIV infection is reportedly associated with an increased permeability of the intestinal epithelium and can cause HIV enteropathy, which occurs independently of opportunistic infections. However, the characteristics of small bowel abnormalities attributable to HIV infection are rarely investigated. In the present study, we assessed the intestinal mucosal changes found in HIV-infected patients and compared them with the mucosa of healthy control subjects using capsule endoscopy (CE). Three of the 27 HIV-infected patients harbored gastrointestinal opportunistic infections and were thus excluded from subsequent analyses...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28400196/association-of-rnaset2-gene-polymorphisms-with-decreased-expression-and-clinical-characteristics-of-severity-in-crohn-s-disease
#7
Rivkah Gonsky, Phillip Fleshner, Richard L Deem, Eva Biener-Ramanujan, Dalin Li, Alka A Potdar, Janine Bilsborough, Shaohong Yang, Dermot P B McGovern, Stephan R Targan
BACKGROUND & AIMS: Variants in the tumor necrosis factor superfamily member 15 gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory bowel diseases (IBD). TL1A affects expression of multiple cytokines to promote mucosal inflammation. Little is known about the TL1A-response pathways that regulate cytokine expression. We investigated T-cell gene expression patterns to determine the mechanisms by which TL1A regulates cytokine production, and whether these associate with outcomes of patients with Crohn's disease (CD)...
April 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28327177/intestinal-t-lymphocyte-homing-is-associated-with-gastric-emptying-and-epithelial-barrier-function-in-critically-ill-a-prospective-observational-study
#8
Christian Greis, Zohal Rasuly, Rolf A Janosi, Lambros Kordelas, Dietrich W Beelen, Tobias Liebregts
BACKGROUND: Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS: We conducted a prospective observational study at two tertiary care medical ICUs...
March 22, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28264908/differences-in-the-importance-of-mast-cells-basophils-ige-and-igg-versus-that-of-cd4-t-cells-and-ilc2-cells-in-primary-and-secondary-immunity-to-strongyloides-venezuelensis
#9
Kaori Mukai, Hajime Karasuyama, Kenji Kabashima, Masato Kubo, Stephen J Galli
There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in Il3-deficient and c-kit mutant Kit(W/W-v) mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis during primary infection. Our findings in mast cell-deficient Kit(W-sh/W-sh) mice and two types of mast cell-deficient mice that have normal c-kit ("Hello Kitty" and MasTRECK mice) confirmed prior work in Kit(W/W-v) mice that suggested that mast cells play an important role in S...
May 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28246016/gut-specific-delivery-of-t-helper-17-cells-reduces-obesity-and%C3%A2-insulin-resistance-in-mice
#10
Chun-Pyo Hong, Areum Park, Bo-Gie Yang, Chang Ho Yun, Min-Jung Kwak, Gil-Woo Lee, Jung-Hwan Kim, Min Seong Jang, Eun-Jung Lee, Eun-Ji Jeun, Gihoon You, Kwang Soon Kim, Youngwoo Choi, Ji-Hwan Park, Daehee Hwang, Sin-Hyeog Im, Jihyun F Kim, Yoon-Keun Kim, Ju-Young Seoh, Charles D Surh, You-Me Kim, Myoung Ho Jang
BACKGROUND & AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4(+) T-helper (TH) cells with obesity and the effects of gut-tropic TH17 cells in mice on a high-fat diet (HFD). METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry...
February 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28220870/long-term-use-of-ceftriaxone-sodium-induced-changes-in-gut-microbiota-and-immune-system
#11
Yanjie Guo, Xuefei Yang, Yane Qi, Shu Wen, Yinhui Liu, Shaoying Tang, Rongsheng Huang, Li Tang
Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities. Previous studies have all focused on the effects of short term use of antibiotics. Here, we focus on the effects of long term use of antibiotic on gut microbiota and immunity. BALB/c mice received saline or different doses of ceftriaxone sodium (100, 200 and 400 mg/mL) via daily gavage for 150 days. Alterations of fecal microbiota, small intestine histopathology, body weight, spleen index, serum IgG, mucus SIgA, IFN-γ/IL-4 ratio, CD4/CD8 ratio and CD4(+)CD25(+) cells were evaluated...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166225/the-composition-of-t-cell-subtypes-in-duodenal-biopsies-are-altered-in-coeliac-disease-patients
#12
Janni V Steenholt, Christian Nielsen, Leen Baudewijn, Anne Staal, Karina S Rasmussen, Hardee J Sabir, Torben Barington, Steffen Husby, Henrik Toft-Hansen
One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+) and the number of CD3+ CD4- CD8- double-negative (DN) T cells were elevated 6-7 fold in children with CD...
2017: PloS One
https://www.readbyqxmd.com/read/28134306/bacterial-translocation-aggravates-ccl4-induced-liver-cirrhosis-by-regulating-cd4-t-cells-in-rats
#13
Haiyan Shi, Longxian Lv, Hongcui Cao, Haifeng Lu, Ning Zhou, Jiezuan Yang, Haiyin Jiang, Huihui Dong, Xinjun Hu, Wei Yu, Xiawei Jiang, Beiwen Zheng, Lanjuan Li
Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3(+)CD4(+)CD25(+)Foxp3(+)), Th17 (CD3(+)CD4(+)IL-17(+)), and Th1 (CD3(+)CD4(+)IFN-γ(+)) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl4. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063048/monitoring-and-modulation-of-inducible-foxp3-regulatory-t-cell-differentiation-in-the-lymph-nodes-draining-the-small-intestine-and-colon
#14
S Veenbergen, L A van Berkel, M F du Pré, A E Kozijn, Janneke N Samsom
The mucosa-draining lymphoid tissue favors differentiation of inducible Foxp3(+) regulatory T cells. Adoptive transfer of T-cell receptor (TCR) transgenic (Tg) T cells is a powerful tool to study antigen-specific regulatory T-cell differentiation in lymphoid tissues in vivo. The kinetics and nature of the T-cell response largely depend on the route of antigen administration and degree of clonal competition. Here, we describe that adoptive transfer of CD4(+) DO11.10 TCR Tg T cells can be used for monitoring Foxp3(+) regulatory T-cell differentiation in the gut-draining lymph nodes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27936497/proinflammatory-cytokine-interferon-%C3%AE-and-microbiome-derived-metabolites-dictate-epigenetic-switch-between-forkhead-box-protein-3-isoforms-in-coeliac-disease
#15
G Serena, S Yan, S Camhi, S Patel, R S Lima, A Sapone, M M Leonard, R Mukherjee, B J Nath, K M Lammers, A Fasano
Coeliac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong T helper type 1 (Th1)/Th17 immune response in the small intestine. Regulatory T cells (Treg ) are CD4(+) CD25(++) forkhead box protein 3 (FoxP3(+) ) cells that regulate the immune response. Conversely to its counterpart, FoxP3 full length (FL), the alternatively spliced isoform FoxP3 Δ2, cannot properly down-regulate the Th17-driven immune response. As the active state of CD has been associated with impairments in Treg cell function, we aimed at determining whether imbalances between FoxP3 isoforms may be associated with the disease...
March 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#16
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926535/high-salt-diet-stimulates-gut-th17-response-and-exacerbates-tnbs-induced-colitis-in-mice
#17
Yingfeng Wei, Chong Lu, Jianing Chen, Guangying Cui, Lin Wang, Tianming Yu, Yue Yang, Wei Wu, Yulong Ding, Lanjuan Li, Toshimitsu Uede, Zhi Chen, Hongyan Diao
This study focuses on characterizing the effect of a high salt diet (HSD) on intestinal immunity and the risk of inflammatory bowel diseases (IBD). We found that mice on a HSD had an increased frequency of IL-17A producing cells in the intestinal lamina propria (LP) compared to mice on a normal diet (ND). Furthermore, most intestinal IL-17A producing cells were CD4+TCRβ+ cells. A HSD increased the LP T helper 17 (Th17) responses in both the small and large intestines but did not increase the Th17 response of other gut-associated lymphoid organ...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27828940/different-tissue-phagocytes-sample-apoptotic-cells-to-direct-distinct-homeostasis-programs
#18
Ryan J Cummings, Gaetan Barbet, Gerold Bongers, Boris M Hartmann, Kyle Gettler, Luciana Muniz, Glaucia C Furtado, Judy Cho, Sergio A Lira, J Magarian Blander
Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear...
November 24, 2016: Nature
https://www.readbyqxmd.com/read/27815529/control-of-inflammation-by-stromal-hedgehog-pathway-activation-restrains-colitis
#19
John J Lee, Michael E Rothenberg, E Scott Seeley, Bryan Zimdahl, Sally Kawano, Wan-Jin Lu, Kunyoo Shin, Tomoyo Sakata-Kato, James K Chen, Maximilian Diehn, Michael F Clarke, Philip A Beachy
Inflammation disrupts tissue architecture and function, thereby contributing to the pathogenesis of diverse diseases; the signals that promote or restrict tissue inflammation thus represent potential targets for therapeutic intervention. Here, we report that genetic or pharmacologic Hedgehog pathway inhibition intensifies colon inflammation (colitis) in mice. Conversely, genetic augmentation of Hedgehog response and systemic small-molecule Hedgehog pathway activation potently ameliorate colitis and restrain initiation and progression of colitis-induced adenocarcinoma...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27805618/eosinophils-are-required-to-suppress-th2-responses-in-peyer-s-patches-during-intestinal-infection-by-nematodes
#20
J Strandmark, S Steinfelder, C Berek, A A Kühl, S Rausch, S Hartmann
Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils...
May 2017: Mucosal Immunology
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