绿脓杆菌MSHA菌毛株菌苗对反复发作性尿路感染的治疗及其机制研究

采用绿脓杆菌ＭＳＨＡ菌毛株菌苗（ＰＡ－ＭＳＨＡ菌苗）治疗了４０例使用抗生素无效的ＲＵＴＩ,取得了满意的疗效,有效率９５％（３８／４０）,治愈率９２．５％（３７／４０）。对其中１８例进行了治疗前后血清抗ＭＳＨＡ菌毛株抗体效价和外周血Ｔ淋巴细胞亚群测定。疗后患者血清中抗ＭＳＨＡ菌毛株抗体效价较疗前增高８～６４倍;同时外周血Ｔ淋巴细胞亚群的比例得到了改善,ＣＤ３＾＋和ＣＤ４＾＋Ｔ细胞的百分率显著提高（Ｐ〈０．０１）,而ＣＤ８＾＋Ｔ细胞的百分率则显著下降（Ｐ〈０．００１）。治疗过程未见明显的副作用。研究表明：ＰＡ－ＭＳＨＡ菌苗对反复发作性尿路感染治愈率高,安全可靠,患者的免疫低下状态得到改善,且对多种病原菌（包括革兰阴性杆菌及其Ｌ型、金黄色葡萄球菌及其Ｌ型）所致的ＲＵＴＩ效果都很好。     

Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases

Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces DCs with a tolerogenic phenotype, characterized by decreased expression of CD40, CD80, and CD86 costimulatory molecules, low IL-12 and enhanced IL-10 secretion. We have found that a short treatment with 1,25(OH)(2)D(3) induces tolerance to fully mismatched mouse islet allografts that is stable to challenge with donor-type spleen cells and allows acceptance of donor-type vascularized heart grafts. This effect is enhanced by co-administration of mycophenolate mofetil (MMF), a selective inhibitor of T and B cell proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft acceptance is associated with an increased percentage of CD4(+)CD25(+) regulatory cells in the spleen and in the draining lymph node that can protect 100% of syngeneic recipients from islet allograft rejection. CD4(+)CD25(+) cells, able to inhibit the T cell response to a pancreatic autoantigen and to significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells, are also induced by treatment of adult nonobese diabetic (NOD) mice with 1,25-dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-698). This treatment arrests progression of insulitis and Th1 cell infiltration, and inhibits diabetes development at non-hypercalcemic doses. The enhancement of CD4(+)CD25(+) regulatory T cells, able to mediate transplantation tolerance and to arrest type 1 diabetes development by a short oral treatment with VDR ligands, suggests possible clinical applications of this approach.     

壳寡糖的制备及其在医学和农业生产中的应用

壳寡糖为一种由2~10个氨基葡萄糖经β-1,4糖苷键连接而成的寡糖聚合物,可通过化学水解或酶降解几丁质或壳聚糖获得,在医学及农业生产等各个领域具有广泛的研究和应用价值。壳寡糖天然无毒,分子量相对较低,水溶性好,易于吸收,且具有良好的生物相容性。此外,壳寡糖也表现出了良好的生物学活性,包括抗肿瘤、抗炎、免疫调节、抗菌、改善糖脂代谢紊乱、保护神经损伤等。对壳寡糖的制备和表征、生物学功能及应用进展进行了综述,并对壳寡糖产业目前存在的问题及未来的研究方向进行了讨论,以期为壳寡糖的深度开发提供依据。     

Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8+ T cells in lipopolysaccharide‐induced acute lung injury in mice

ObjectivesAcute lung injury (ALI) not only affects pulmonary function but also leads to intestinal dysfunction, which in turn contributes to ALI. Mesenchymal stem cell (MSC) transplantation can be a potential strategy in the treatment of ALI. However, the mechanisms of synergistic regulatory effects by MSCs on the lung and intestine in ALI need more in‐depth study.Materials and methodsWe evaluated the therapeutic effects of MSCs on the murine model of lipopolysaccharide (LPS)‐induced ALI through survival rate, histopathology and bronchoalveolar lavage fluid. Metagenomic sequencing was performed to assess the gut microbiota. The levels of pulmonary and intestinal inflammation and immune response were assessed by analysing cytokine expression and flow cytometry.ResultsMesenchymal stem cells significantly improved the survival rate of mice with ALI, alleviated histopathological lung damage, improved intestinal barrier integrity, and reduced the levels of inflammatory cytokines in the lung and gut. Furthermore, MSCs inhibited the inflammatory response by decreasing the infiltration of CD8⁺ T cells in both small‐intestinal lymphocytes and Peyer''s patches. The gut bacterial community diversity was significantly altered by MSC transplantation. Furthermore, depletion of intestinal bacterial communities with antibiotics resulted in more severe lung and gut damages and mortality, while MSCs significantly alleviated lung injury due to their immunosuppressive effect.ConclusionsThe present research indicates that MSCs attenuate lung and gut injury partly via regulation of the immune response in the lungs and intestines and gut microbiota, providing new insights into the mechanisms underlying the therapeutic effects of MSC treatment for LPS‐induced ALI.     

Senescent immune cells release grancalcin to promote skeletal aging

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Antimicrobial and immunoregulatory effects mediated by human lung cells: role of IFN-γ-induced tryptophan degradation

Pneumonia caused by bacterial, viral and parasitic pathogens is one of the most common clinical problems facing primary and secondary care physicians. Staphylococcus aureus is a common cause of lung abscesses in humans and, in immunocompromised patients, herpes simplex virus type I and Toxoplasma gondii can cause severe life-threatening pneumonia. The authors focused their interest in the antimicrobial effects mediated by human lung cells against these pathogens. It was found that IFN-γ-stimulated lung cells are capable of inhibiting T cell proliferation and restrict the replication of microorganisms such as T. gondii , S. aureus and herpes simplex virus. This immunoregulatory and antimicrobial effect was enhanced in the presence of IL-1 or tumor necrosis factor-α (TNF-α). Furthermore, the IFN-γ-dependent antimicrobial effects of HBE4-E6/E7 (human lung bronchus epithelial cells) and A549 (human type II alveolar cells) correlated with the activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). It was found that both the abrogation of IDO activity by the specific IDO-inhibitor 1- l -methyltryptophan and the supplementation of cultures with tryptophan result in an inhibition of IFN-γ-induced antimicrobial effects mediated by lung cells. Therefore it is suggested that tryptophan depletion via IFN-γ-mediated IDO induction is a major antibacterial, antiparasitic, antiviral and immunoregulatory mechanism in human lung cells.     

Schistosoma mansoni: Permanence of modulation of the granulomatous inflammatory response in mice cured in the chronic phase

Persistence of down regulation of granoloma size was studied in mice chronically infected with Schistosoma mansoni and cured by chemotherapy. The animals were reinfected at 20-, 50-, 110- and 140-day intervals after treatment, and sacrificed 60 days post-reinfection. Reinfected animals were able to modulate the granulomatous inflammatory response, thus preventing a new acute phase. These findings may contribute to the explanation for the decrease of morbidity from human schistosomiasis seen in endemic areas following mass treatment.     

Characterization of OP9 as authentic mesenchymal stem cell line

Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into various cell types,including osteocytes,chondrocytes,adipocytes,myocytes,and tenocytes.However,the difficulty or failure in expanding the mouse MSCs in vitro greatly hampered important research in animal models.The OP9,a stromal cell line from mouse bone marrow,has hematopoietic supportive capacity.Here,we report that the OP9 has the immunophenotype (CD45-,CD11b-,FLK-1-,CD31-,CD34-,CD44+,CD29+,Sca-1+,CD86-,and MHCII-) identical to canonical mouse MSCs.The expression of CD140a+,CD140b+,α-SMA+ and Calponin+ suggested the perivascular origin of OP9.Functionally,the OP9 had strong clonogenic ability and could be induced into osteocytes,chondrocytes and adipocytes.The lymphocyte transformation test (LTT) and mixed leukocyte reaction (MLR) showed that the OP9 could suppress T lymphocyte proliferation stimulated by nonspecific mitogens (PHA) or allogeneic lymphocytes (BALB/c T cells).Finally,the migration of OP9 could be efficiently induced by bFGF,IGF-1,IL-3,PDGF-BB,TGF-β1 and TGF-β3.In conclusion,the OP9 were bona fide MSCs,and such homogenous cell line will be helpful to delineate biological features of MSCs at the stem cell level.