Class I/II hybrid inhibitory oligodeoxynucleotide exerts Th1 and Th2 double immunosuppression

We designed class I/II hybrid inhibitory oligodeoxynucleotides (iODNs), called iSG, and found that the sequence 5′-TTAGGG-3′, which has a six-base loop head structure, and a 3′-oligo (dG)3–5 tail sequence are important for potent immunosuppressive activity. Interestingly, splenocytes isolated from ovalbumin (OVA)-immunized mice and treated with iSG3 showed suppression of not only interleukin (IL)-6, IL-12p35, IL-12p40, and interferon (IFN) γ mRNA expression, but also IL-4 and IL-13 mRNA expression. Thus, both Th2 and Th1 immune responses can be strongly suppressed by iODNs in splenocytes from allergen-immunized mice, suggesting usefulness in the treatment of diseases induced by over-active immune activation.ArticleFEBS Open Bio. 3:41-45 (2013)journal articl

Pyogenic Ventriculitis After Anterior Skull Base Surgery Treated With Endoscopic Ventricular Irrigation And Reconstruction Using a Vascularized Flap

Ventriculitis is a rare, serious complication of neurosurgery. A 59-year-old man who had undergone a craniotomy for a paranasal adenocarcinoma, developed a right frontal cystic lesion. We performed a bifrontal craniotomy to remove the lesion. The dura was repaired with non-vascularized free fascia lata in watertight fashion. Ventriculitis occurred 3 days postoperatively. Ventricular drainage, craniectomy, and endoscopic irrigation were undertaken to remove an abscess. The dura and the resection cavity were reconstructed using a vascularized anterolateral thigh adipofascial flap. His symptoms disappeared, indicating that endoscopic irrigation and reconstruction can effectively address ventriculitis even in patients in critical clinical condition

Effect of dietary supplementation of immunobiotic lactiplantibacillus plantarum n14 fermented rakkyo (Allium chinense) pickled juice on the immunocompetence and production performance of pigs

Rakkyo (Allium chinense), is a Japanese leek that is primarily used to make a popular sweet or sour pickled dish. Lactic acid bacteria are often involved in the preparation steps of fermented pickles, which helps in the effective preservation of the natural bioactive compounds of fruits and vegetable, and thereby exert several health benefits including immunomodulation and growth per-formance. This work aimed to evaluate the in vivo effects of adding Lactiplantibacillus plantarum N14 fermented rakkyo pickled juice as feed supplement on the immunocompetence and production performance of pigs. We first analyzed the nutritional composition, which revealed that the proportion of protein, lipid, and water-soluble fiber content were estimated as of 4%, 5%, and 5% in rakkyo residual liquid or juice, while 22%, 15% and 14%, respectively, were estimated in rakkyo residual powder. For the in vivo feeding trials, three groups of pigs were treated either with 5%, 20%, or 40% mixture (v/v) of fermented rakkyo pickled juice and the grinded residual liquid supplemented in the drinking water in addition to standard feed. The results of the feeding trials showed that the administration of a juice mixture of 5% or 20% (fermented pickled juice and residual liquid) had a similar trend of effects in improving the complement activity, phagocytic activity and leucocytes counts in the peripheral blood when compared to pigs fed with 40% mixture or untreated controls. Those changes were related to an improved resistance to enteric infections. Moreover, animals receiving a mixture of fermented pickled juice and fermented rakkyo residues had a higher growth rate and carcass quality than controls. The results suggested that the use of 5% mixture of fermented rakkyo pickled juice and the residual liquid through drinking water could be a cost-effective approach to promote the immune-health and production performance of pigs. This approach would contribute not only to the sustainable management of food wastes but also to the application of a value-added feed supplement for the promotion of animal health and production.Fil: Islam, Md Aminul. Tohoku University; Japón. Bangladesh Agricultural University; BangladeshFil: Hashiguchi, Kenji. No especifíca;Fil: Humayun Kober, A.K.M.. Tohoku University; Japón. Chittagong Veterinary and Animal Sciences University; BangladeshFil: Morie, Kyoko. Tohoku University; JapónFil: Zhou, Binghui. Tohoku University; JapónFil: Tomokiyo, Mikado. Tohoku University; JapónFil: Shimazu, Tomoyuki. Miyagi University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Suda, Yoshihito. Miyagi University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs

Background: Immunoregulatory probiotics (immunobiotics) have been proposed to improve piglets' immune system to avoid intestinal infections and reduce unproductive inflammation after weaning. Previously, it was demonstrated that Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer's patches (PP).Objective: In view of the critical importance of PIE-APCs interactions in the regulation of intestinal immune responses, we aimed to examine the effect of LjTL2937 on activation patterns of APCs from swine PPs in co-cultures with PIE cells. In addition, we investigated whether LjTL2937 was able to beneficially modulate intestinal immunity of piglets after weaning to improve immune-health status.Results: Stimulation of PIE-APCs co-cultures with LjTL2937 increased the expression of MHC-II, CD80/86, IL-10, and Bcl-3 in CD172a+CD11R1- and CD172a+CD11R1high APCs. In addition, the TL2937 strain caused the upregulation of three negative regulators of TLR4 in PIE cells: MKP-1, Bcl-3 and A20. These changes significantly reduced the inflammatory response triggered by TLR4 activation in PIE-APCs co-cultures. The in vivo experiments using castrated male piglets (crossbreeding (LWD) with Landrace (L), Large Yorkshire (W) and Duroc (D))of 3 weeks of age demonstrated that feeding with LjTL2937 significantly reduced blood complement activity and C reactive protein concentrations while no changes were observed in blood leukocytes, ratio of granulocytes to lymphocyte numbers, macrophages' activity and antibody levels. In addition, treatment with LjTL2937 significantly improved growth performance and productivity, and increased carcass quality.Conclusions: We demonstrated that the use of immunobiotics strains like LjTL2937, as supplemental additives for piglets feedings, could be used as a strategy to maintain and improve intestinal homeostasis; that is important for the development of the pig and for health and performance throughout the productive life of the animal.Fil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Takahashi, Yu. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Hosoya, Shoichi. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Tsukida, Kohichiro. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Shimazu, Tomoyuki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Breading and Genetics ; JapónFil: Aso, Hisashi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; JapónFil: Tohno, Masanori. National Institute of Livestock and Grassland Science; JapónFil: Ishida, Mitsuharu. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Makino, Seiya. No especifíca;Fil: Ikegami, Shuji. No especifíca;Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japó

Bifidobacteria upregulate expression of toll-like receptor negative regulators counteracting enterotoxigenic Escherichia coli mediated inflammation in bovine intestinal epitheliocytes

We previously established a bovine intestinal epithelial cell line (BIE cells) and showed that BIE cells are useful in vitro model system for the study of interactions between pathogenic and beneficial microorganisms and bovine intestinal epithelial cells (IECs). In the present study we aimed to select potential immunomodulatory bifidobacteria that may be used to beneficially modulate the inflammatory response in bovine IECs. We also aimed to gain insight in the molecular mechanisms involved in the anti-inflammatory effect of bifidobacteria by evaluating the role of Toll-like receptor (TLR)-2 and TLR negative regulators in the regulation of proinflamatory cytokines production and MAPK, NF-κB and PI3K pathways activation in BIE cells. Five bifidobacteria strains were evaluated in this study and according to their capacity to modulate inflammatory response of BIE cells. Despite the unique effect of each strain, four common points were found when comparing the effect of the high and moderate anti-inflammatory strains: 1) Upregulation of TLR negative regulators and the intensity of that upregulation was related to the different immunomodulatory capacity of each bifidobacteria strain. 2) The balance between MAPK activation and MKP-1 upregulation affected the an- ti-inflammatory effect of bifidobacteria in BIE cells. 3) The inhibition of PI3K pathway was related to the an- ti-inflammatory effect of bifidobacteria. 4) The immunoregulatory effect of bifidobacteria in BIE cells is partially de- pendent on TLR2. This study shows that BIE cells can be used for the selection of immunoregulatory bifidobacteria and for studying the mechanisms involved in the protective activity of immunobiotics against TLR4-induced inflammatory damage. In addition, we have demonstrated that the anti-inflammatory effect of bifidobacteria was achieved by a com- plex interaction of multiple TLRs negative regulators as well as the inhibition/activation of multiple signaling pathways.Fil: Murata, Kozue. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Risa, Hara. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Chiba, Eriko. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Shimazu, Tomoyuki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Breeding and Genetics; Japón;Fil: Aso, Hisashi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; Japón;Fil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environmental Science; Japón;Fil: Iwabuchi, Noriyuki. Morinaga Milk Industry Co. Ltd. Food Science and Technology Institute; Japón;Fil: Xiao, Jin-zhong. Morinaga Milk Industry Co. Ltd. Food Science and Technology Institute; Japón;Fil: Saito, Tadao. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón;Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japón

Immunobiotic lactic acid bacteria beneficially regulate immune response triggered by poly(I:C) in porcine intestinal epithelial cells

This study analyzed the functional expression of TLR3 in various gastrointestinal tissues from adult swine and shows that TLR3 is expressed preferentially in intestinal epithelial cells (IEC), CD172a+CD11R1high and CD4+ cells from ileal Peyer's patches. We characterized the inflammatory immune response triggered by TLR3 activation in a clonal porcine intestinal epitheliocyte cell line (PIE cells) and in PIE-immune cell co-cultures, and demonstrated that these systems are valuable tools to study in vitro the immune response triggered by TLR3 on IEC and the interaction between IEC and immune cells. In addition, we selected an immunobiotic lactic acid bacteria strain, Lactobacillus casei MEP221106, able to beneficially regulate the anti-viral immune response triggered by poly(I:C) stimulation in PIE cells. Moreover, we deepened our understanding of the possible mechanisms of immunobiotic action by demonstrating that L. casei MEP221106 modulates the interaction between IEC and immune cells during the generation of a TLR3-mediated immune response

Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenicEscherichia coli-mediated inflammation

Background: Previously, a bovine intestinal epithelial cell line (BIE cells) was successfully established. This work hypothesized that BIE cells are useful in vitro model system for the study of interactions of microbial- or pathogenassociated molecular patterns (MAMPs or PAMPs) with bovine intestinal epithelial cells and for the selection of immunoregulatory lactic acid bacteria (LAB). Results: All toll-like receptor (TLR) genes were expressed in BIE cells, being TLR4 one of the most strongly expressed. We demonstrated that heat-stable PAMPs of enterotoxigenic Escherichia coli (ETEC) significantly enhanced the production of IL-6, IL-8, IL-1! and MCP-1 in BIE cells by activating both NF-"B and MAPK pathways. We evaluated the capacity of several lactobacilli strains to modulate heat-stable ETEC PAMPs-mediated inflammatory response in BIE cells. Among these strains evaluated, Lactobacillus casei OLL2768 attenuated heat-stable ETEC PAMPs-induced pro-inflammatory response by inhibiting NF-"B and p38 signaling pathways in BIE cells. Moreover, L. casei OLL2768 negatively regulated TLR4 signaling in BIE cells by up-regulating Toll interacting protein (Tollip) and B-cell lymphoma 3-encoded protein (Bcl-3). Conclusions: BIE cells are suitable for the selection of immunoregulatory LAB and for studying the mechanisms involved in the protective activity of immunobiotics against pathogen-induced inflammatory damage. In addition, we showed that L. casei OLL2768 functionally modulate the bovine intestinal epithelium by attenuating heat-stable ETEC PAMPs-induced inflammation. Therefore L. casei OLL2768 is a good candidate for in vivo studying the protective effect of LAB against intestinal inflammatory damage induced by ETEC infection or heat-stable ETEC PAMPs challenge in the bovine host.Fil: Takanashi, Naoya. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tomosada, Yohsuke. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia Para Lactobacilos (i); Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Murata, Kozue. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Takahashi, Takuya. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Chiba, Eriko. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tohno, Masanori. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan; National Agriculture and Food Research Organization. National Institute of Livestock and Grassland Science; Japan.;Fil: Tomoyuki Shimazu. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan; Laboratory of Animal Breading and Genetics. Graduate School of Agricultural Science; Japan.;Fil: Aso, Hisashi. Cell Biology Laboratory, Graduate School of Agricultural Science. Tohoku University; Japan.;Fil: Suda, Yoshihito. Department of Food, Agriculture and Environment. Miyagi University; Japan.;Fil: Ikegami, Shuji. Division of Research and Development. Food Science Institut. Meiji Dairies CoOdawara; Japan;Fil: Itoh, Hiroyuki. Division of Research and Development. Food Science Institut. Meiji Dairies CoOdawara; Japan;Fil: Kawai, Yasushi. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tadao Saito. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Kitazawa, Haruki. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan

Immunobiotic feed developed with Lactobacillus delbrueckii subsp. delbrueckii TUA4408L and the soymilk by-product okara improves health and growth performance in pigs

Lactobacillus delbrueckii subsp. delbrueckii TUA4408L is able to differentially modulate the innate immune response of porcine intestinal epithelial cells triggered by TLR4 activation. This strain also has a remarkable ability to grow on plant substrates. These two immunological and biotechnological characteristics prompted us to evaluate whether the soymilk by-product okara fermented with the TUA4408L strain can serve as an immunobiotic feed with the ability to beneficially modulate the intestinal immunity of piglets after weaning to improve their productivity. Our in vivo studies demonstrated that the administration of immunobiotic TUA4408L-fermented okara feed significantly increased piglet growth performance and meat quality. These positive effects were associated with the ability of the TUA4408L-fermented okara feed to beneficially modulate both intestinal microbiota and immunity in pigs. The immunobiotic feed improved the abundance of the beneficial bacteria Lactobacillus and Lactococcus in the gut of pigs, reduced blood markers of inflammation, and differentially regulated the expression of inflammatory and regulatory cytokines in the intestinal mucosa. These findings indicate that the immunobiotic TUA4408L-fermented okara feed could be an economical and environmentally friendly option to improve the growth performance and immune health of pigs.Fil: Suda, Yoshihito. Miyagi University; JapónFil: Sasaki, Nana. Miyagi University; JapónFil: Kagawa, Kyoma. Miyagi University; JapónFil: Elean, Mariano Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Zhou, Binghui. Tohoku University; JapónFil: Tomokiyo, Mikado. Tohoku University; JapónFil: Islam, Md Aminul. Tohoku University; Japón. Bangladesh Agricultural University; BangladeshFil: Shahid Riaz Rajoka, Muhammad. Tohoku University; JapónFil: Humayun Kober, A.K.M.. Tohoku University; Japón. Chittagong Veterinary and Animal Sciences University; BangladeshFil: Shimazu, Tomoyuki. Miyagi University; JapónFil: Egusa, Shintaro. No especifíca;Fil: Terashima, Yuji. No especifíca;Fil: Aso, Hisashi. Tohoku University; JapónFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kitazawa, Haruki. Tohoku University; Japó