Suppression of Plant Immunity by Fungal Chitinase-like Effectors

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Suppression of Rice Immunity by Xanthomonas oryzae Type III Effector Xoo2875

Single-stranded plasmid DNA of pPF1 from Phormidium foveolarum that was specifically degraded by S1 nuclease was detected by Southern hybridization. This is also the case of the homologous plasmid pPBl from Plectonema boryanum. These observations suggest that such small cryptic plasmids as pPF1 and pPB1, both from Gram-negative and filamentous cyanobacteria, replicate by a rolling circle mechanism in their living cells.     

Suppression of Cell-Mediated Immunity following Recognition of Phagosome-Confined Bacteria

Listeria monocytogenes is a facultative intracellular pathogen capable of inducing a robust cell-mediated immune response to sub-lethal infection. The capacity of L. monocytogenes to escape from the phagosome and enter the host cell cytosol is paramount for the induction of long-lived CD8 T cell–mediated protective immunity. Here, we show that the impaired T cell response to L. monocytogenes confined within a phagosome is not merely a consequence of inefficient antigen presentation, but is the result of direct suppression of the adaptive response. This suppression limited not only the adaptive response to vacuole-confined L. monocytogenes, but negated the response to bacteria within the cytosol. Co-infection with phagosome-confined and cytosolic L. monocytogenes prevented the generation of acquired immunity and limited expansion of antigen-specific T cells relative to the cytosolic L. monocytogenes strain alone. Bacteria confined to a phagosome suppressed the production of pro-inflammatory cytokines and led to the rapid MyD88-dependent production of IL-10. Blockade of the IL-10 receptor or the absence of MyD88 during primary infection restored protective immunity. Our studies demonstrate that the presence of microbes within a phagosome can directly impact the innate and adaptive immune response by antagonizing the signaling pathways necessary for inflammation and the generation of protective CD8 T cells.     

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat.     

Inhibition of Aspartate Transcarbamylase by a Phenobarbital Derivative

Mammalian and hepatic aspartate transcarbamylase is inhibited by phenobarbital p-nitrophenylhydra-zone in a reversible and non-competitive type with K_i values 8.45 × 10^?5 and 9.64×10^?5 M in the reactions toward carbamyl phosphate and aspartate, respectively. In vivo inhibition occurred in a dose-dependent manner in which less than 50% of the activity was retained. These observations suggest that this inhibitor may interfere with the in vivo regulation of this enzyme and lead to an additional biological effect of phenobarbitals.     

Suppression of Erythropoiesis by Alcohol

Serial measurements in alcoholic subjects showed a profound fall of serum iron for three days after withdrawal of alcohol and a reversion of abnormal accumulation of erythroblastic haemosiderin to normal. These findings suggest an interference in normal haem synthesis, most probably by a direct effect.     

Immunity to herpes simplex virus type 2. Suppression of virus-induced immune responses in ultraviolet B-irradiated mice

Ultraviolet B irradiation (280 to 320 nm) of mice at the site of intradermal infection with herpes simplex virus type 2 increased the severity of the herpes simplex virus type 2 disease and decreased delayed-type hypersensitivity (DTH) responses to viral antigen. Decrease in DTH resulted from the induction of suppressor T cells, as evidenced by the ability of spleen cells from UV-irradiated mice to inhibit DTH and proliferative responses after adoptive transfer. Lymph node cells from UV-irradiated animals did not transfer suppression. DTH was suppressed at the induction but not the expression phase. Suppressor T cells were Lyt-1+, L3T4+, and their activity was antigen-specific. However, after in vitro culture of spleen cells from UV-irradiated mice with herpes simplex virus type 2 antigen, suppressor activity was mediated by Lyt-2+ cells. Culture supernatants contained soluble nonantigen-specific suppressive factors.     

Phenobarbital stimulation of housefly chromatin template activity

The effect of phenobarbital on the chemical composition and template activity for Escherichia coli RNA polymerase of housefly chromatin is examined. Chromatin isolated from the resistant Fc housefly strain after administration of phenobarbital has a much higher template activity as compared to control chromatin. The effect is minimal in a susceptible housefly strain. Phenobarbital treatment alters the composition of the RNA polymerase product which results in an increase of the $\text{(A + U)}\text{(C + G)}$ ratio with chromatin from the Fc strain as template, while the $\text{(A + G}\text{)}\text{(}\text{C + U)}$ and $\text{(A + U}\text{)}\text{(}\text{C + G)}$ ratios are decreased when chromatin of the susceptible strain is used.A substantial portion of the intracellular phenobarbital is physically bound to nuclei and microsomes, but most of it is associated with cytosolic macromolecules. Less than 0.2% is covalently bound to cellular macromolecules. Phenobarbital apparently binds to a small mol. wt cytosolic macromolecule(s) as shown by sucrose density gradient centrifugation and Sephadex G-25 column chromatography.     

MicroRNA 对获得性免疫的调节作用

微RNA(MicroRNA,miRNA)是一类在转录后水平调节基因表达的大约22 nt的非编 码内源单链RNA.已经表明,它们与许多重要的生理和病理过程相关,包括发育、分化、细胞 凋亡、脂肪代谢、病毒感染和癌症.越来越多的证据表明,miRNA参与了获得性免疫的调节. 有趣的是,不同于开关式的调节,miRNA表现出定量的基因调节,它们能精细调节细胞免疫 反应以响应外界刺激.深入理解miRNAs对获得性免疫的调节作用有助于调节宿主免疫应答和 保护感染组织间的平衡,鉴定免疫调节新靶标和开发基于miRNA的有效疗法.本文综述了miRN A包括病毒miRNA对获得性免疫的调节作用,特别是miRNA在调节免疫活性细胞、T细胞功 能和抗体产生中的作用.     

Toll样受体与树突状细胞介导的天然免疫和获得性免疫

树突状细胞(dendritic cells,DCs)作为迄今所发现的抗原提呈功能最强的一类抗原提呈细胞,是联结天然免疫和获得性免疫的桥梁。Toll样受体(Toll-like receptors,TLRs)是一类进化保守的胚系编码的模式识别受体,在DCs的抗原识别、递呈及激活T细胞等方面具有重要作用,是机体受外来抗原入侵后作出适当免疫反应的调控点。现就TLRs在不同DCs亚群中的分布、与DCs介导的天然免疫和获得性免疫的关系及DCs功能可塑性的分子基础作一综述。     

Circadian Time-Dependent Kinetics of Theophylline and Its Modulation by Phenobarbital Pretreatment in Rats

The pharmacokinetics of theophylline (TPH, 10 mg/kg i.v.) were assessed in rats (natural light-dark span, June 9–10) after i.p. pretreatment with saline and 80 mg/kg phenobarbital (PB), respectively, for 3 consecutive days at either 07:00 h or at 19:000 h. Serum concentrations of TPH were assayed by high-performance liquid chromatography. No significant differences of the elimination rates of TPH could be found between the times of TPH administration (clearance: 1.17 ± 0.17 ml/kg/min at 07:00 h vs. 1.23 ± 0.17 ml/kg/min at 19:00 hours). PB premedication markedly accelerated TPH elimination. The increase in clearance values was more expressed when TPH was injected at 07:00 h than at 19:00 h (2.48 ± 0.67 vs. 2.06 ± 0.41 ml/kg/min, p < 0.01).     

Suppression of insulin aggregation by heparin

The aggregation of insulin near its isoelectric point and at low ionic strength was suppressed in the presence of heparin. To understand this effect, we used turbidimetry and stopped-flow to study the pH- and ionic strength ( I)-dependence of the aggregation of heparin-free insulin. The results supported the role of interprotein electrostatic interactions, contrary to the commonly held view that such forces are minimized at pH = pI. Electrostatic modeling of insulin (DelPhi) revealed that attractive interactions arise from the marked charge anisotropy of insulin near pI. We show how screening of the interprotein attractions by added salt lead to maximum aggregation near I = 0.01 M, corresponding to a Debye length nearly equal to the diameter of the insulin dimer, consistent with a dipole-like protein charge distribution. This analysis is also consistent with suppression of aggregation by heparin, a strong polyanion that by binding to the positive domain of one protein, inhibits its interaction with the negative domain of another.