TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification

Host protection from infection relies on the recognition of pathogens by innate pattern-recognition receptors such as Toll-like receptors (TLRs). Here, we show that the orphan receptor TLR13 in mice recognizes a conserved 23S ribosomal RNA (rRNA) sequence that is the binding site of macrolide, lincosamide, and streptogramin group (MLS) antibiotics (including erythromycin) in bacteria. Notably, 23S rRNA from clinical isolates of erythromycin-resistant Staphylococcus aureus and synthetic oligoribonucleotides carrying methylated adenosine or a guanosine mimicking a MLS resistance-causing modification failed to stimulate TLR13. Thus, our results reveal both a natural TLR13 ligand and specific mechanisms of antibiotic resistance as potent bacterial immune evasion strategy, avoiding recognition via TLR13.     

Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2

beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.     

A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence

Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration approximately 100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor-based therapy against S. aureus.     

栓皮栎树皮对溶液中重金属离子吸附性能的研究

[目的]开发研制出高容量、低成本的重金属离子生物吸附剂。[方法]以连云港本土的栓皮栎树皮为原料,对树皮进行改性,研究其对重金属离子的吸附性能,对水中Cr6+、Mg2+、Cu2+进行了吸附试验,探讨了吸附时间、pH、吸附温度、原溶液的浓度、吸附剂用量等因素对改性吸附剂吸附Cr6+、Mg2+、Cu2+的影响。[结果]试验表明,以栓皮栎树皮制得的吸附剂具有较强的螯合和吸附作用,能有效吸附Cr6+、Mg2+、Cu2+离子,且价格低廉,应用前景广阔。同时,为解决原位固化栓皮栎树皮对Cu2+等离子吸附容量小的问题,进一步对原位固化栓皮栎树皮氧化改性,考察其对金属离子,特别是Cu2+的吸附容量以及影响吸附的因素。[结论]以栓皮栎树皮为原料可研制出对溶液中重金属离子吸附性能较好的生物吸附剂。     

芡种壳多酚超声辅助提取工艺优化及其对金黄色葡萄球菌的抑制效果

【目的】优化芡种壳多酚提取工艺,并分析其对金黄色葡萄球菌的抑制作用和抑菌稳定性,为芡种壳的资源化利用提供参考依据。【方法】采用超声辅助法提取芡种壳多酚,以多酚提取率（Y）为评价指标,对超声时间（X₁）、超声温度（X₂）和料液比（X₃）3个因素进行单因素和响应面试验,确定最佳提取工艺,初步纯化;采用琼脂扩散法研究芡种壳多酚对金黄色葡萄球菌的抑制活性,并测定最小抑菌浓度（MIC）,同时考察温度、pH及金属离子浓度对芡种壳多酚稳定性的影响。【结果】3个因素对芡种壳多酚提取率影响的大小为:超声温度>料液比>超声时间,料液比及超声温度与料液比的交互作用对芡种壳多酚提取率有显著影响（P< 0.05）,超声温度对多酚提取率有极显著影响（P< 0.01）。得到回归方程Y=14.57+0.064X₁+0.26X₂+0.11X₃+0.079X₁X₂-0.018X₁X₃-0.18X₂X₃-0.11X₁2-0.54X₂2-0.19X₃2;最佳提取工艺为:超声时间39 min、超声温度72 ℃、料液比1:41,在此条件下,芡种壳多酚提取率为14.479%,与预测值（14.630%）接近;芡种壳多酚对金黄色葡萄球菌具有明显抑制作用,MIC为0.1625 mg/mL;温度及Ca2+、Mg2+、K+、Na+4种金属离子对芡种壳多酚抑制金黄色葡萄球菌活性不具有显著影响（P> 0.05）,而随着pH的增加,芡种壳多酚抑菌活性受到抑制。【结论】采用优化的超声辅助法可有效提取芡种壳中多酚物质,提取到的多酚对金黄色葡萄球菌的生长具有良好且较稳定的抑制效果。     

免疫系统对营养代谢的调节

 营养和免疫的相互作用多种多样,对动物的生长和生产有着深远的影响。天然免疫系统在感染初期对机体提供保护, 同时调节很多营养代谢的变化。巨噬细胞是天然免疫细胞的主要感觉和调节细胞。前炎症细胞因子不仅针对病原体调整局部免疫,而且也改变全身代谢的动态平衡,降低采食量和生长率, 能量、氨基酸、脂肪与矿物质代谢的改变具有重要的营养意义。免疫系统产生的调节因子可改变全身的营养分配和阻止与生长有关的代谢过程。论述了在免疫应答中,能量、氨基酸、脂肪和微量元素代谢在数量方面的重要变化。     

PRRSV逃逸宿主天然免疫的分子机制

猪繁殖与呼吸综合症病毒（PRRSV）可破坏机体的天然免疫系统,导致猪的免疫抑制,进而导致继发感染或混合感染,为进一步研究PRRSV逃逸宿主天然免疫的分子机制,综述了PRRSV抑制I型IFN的激活及其相关信号通路,逃逸宿主天然免疫系统的多种途径,从而避免PRRSV侵染,为PRRSV的防控提供分子基础。     

雏鸡感染传染性法氏囊病毒后血液的T细胞变化

本项研究对雏鸡感染传染性法氏囊病毒(IBDV)后,1～8周外周血液的 ANAE~+淋巴细胞(T 细胞)、淋巴细胞和白细胞数量的动态变化进行了检测。结果表明,1日龄雏鸡感染 IBDV 后,其血液中 ANAE~+,淋巴细胞数量明显低于对照雏鸡,表明其细胞免疫机能降低;4周龄雏鸡感染 IBDV 后,其 ANAE~+淋巴细胞数量呈一过性降低,变化不如1日龄感染雏鸡明显,说明 IBDV 对雏鸡存在感染年龄差异;对 ANAE~+淋巴细胞绝对数的检测较百分比能更真实地反映 IBD 鸡的细胞免疫功能变化的实质。     

New paradigms in type 2 immunity

Nearly half of the world's population harbors helminth infections or suffers from allergic disorders. A common feature of this population is the so-called "type 2 immune response," which confers protection against helminths, but also promotes pathologic responses associated with allergic inflammation. However, the mechanisms that initiate and control type 2 responses remain enigmatic. Recent advances have revealed a role for the innate immune system in orchestrating type 2 responses against a bewildering array of stimuli, from nanometer-sized allergens to 20-meter-long helminth parasites. Here, we review these advances and suggest that the human immune system has evolved multiple mechanisms of sensing such stimuli, from recognition of molecular patterns via innate immune receptors to detecting metabolic changes and tissue damage caused by these stimuli.     

Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation

A defining feature of inflammation is the accumulation of innate immune cells in the tissue that are thought to be recruited from the blood. We reveal that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under the control of the archetypal T(H)2 cytokine interleukin-4 (IL-4) and was a fundamental component of T(H)2 inflammation because exogenous IL-4 was sufficient to drive accumulation of tissue macrophages through self-renewal. Thus, expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells.     

企业文化就是一言一行

几年前,中国企业家调查系统在对2881位企业经营者做出的问卷调查表明,有60．1％的人同意“企业文化是企业发展到一定阶段才形成的”这一说法。     

水稻根系对镧、铈、锌胁迫的生理生化应答(英文)

[目的]研究镧(La3+)、铈(Ce3+)、锌(Zn2+)对水稻根系的生理生化影响,探讨过量施用稀土的环境效应。[方法]以稀土元素镧(La3+)、铈(Ce3+)和兼具营养与毒性的重金属元素锌(Zn2+)为胁迫因子,采用组织培养法比较三者对水稻种子萌发及幼苗生长发育的影响。[结果]La3+、Ce3+和Zn2+对水稻种子萌发率影响很小,但对幼苗根、苗的生长具有显著的抑制作用,且在高浓度下稀土离子的抑制作用均大于Zn2+。水稻根可溶蛋白质含量随3种金属离子浓度的升高均呈先升后降的趋势,且La3+、Ce3+较Zn2+更为敏感;CAT和POD的活性随La3+、Ce3+和Zn2+浓度的增加逐渐上升,而SOD活性则先降后升;3种金属离子均能显著地刺激水稻根内MDA迅速积累。在高浓度下,La3+、Ce3+表现出比Zn2+更强的毒性。[结论]稀土元素La3+、Ce3+同重金属元素Zn2+对水稻的毒害机制相似。从长远来看,稀土有可能是一种新型的污染。     

鸡白细胞介素18研究进展

鸡白细胞介素(IL-18)是一种新发现的细胞因子,其cDNA全长597 bp,编码198个氨基酸的前体多肽,分子量约为23 kDa,IL-18氨基端的29个氨基酸残基起胞内定位作用;鸡IL-18是IFN-γ诱生剂,通过IFN-γ发挥抗感染、促生长等作用,参与对微生物感染诱导产生细胞和体液免疫反应的初次免疫应答;鸡IL-18作为免疫佐剂,具有增强免疫和治疗作用,还具有抗肿瘤免疫作用。     

Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection

Certain pathogens, such as Mycobacterium tuberculosis, survive within the hostile intracellular environment of a macrophage. To identify host factors required for mycobacterial entry and survival within macrophages, we performed a genomewide RNA interference screen in Drosophila macrophage-like cells, using Mycobacterium fortuitum. We identified factors required for general phagocytosis, as well as those needed specifically for mycobacterial infection. One specific factor, Peste (Pes), is a CD36 family member required for uptake of mycobacteria, but not Escherichia coli or Staphylococcus aureus. Moreover, mammalian class B scavenger receptors (SRs) conferred uptake of bacteria into nonphagocytic cells, with SR-BI and SR-BII uniquely mediating uptake of M. fortuitum, which suggests a conserved role for class B SRs in pattern recognition and innate immunity.     

重金属胁迫培养对微生物生长的影响

为探究重金属胁迫对微生物生长的影响,以大肠杆菌、枯草芽孢杆菌、啤酒酵母菌和链霉菌为材料,用传统微生物培养方法,研究了不同Hg2+、Cd2+、Cr6+和Pb2+浓度下4种微生物的生长状况。结果表明:低浓度重金属离子对4种微生物生长有促进作用,高浓度有抑制作用,G+较G-对Hg2+和Cd2+更为敏感;4种微生物对重金属离子的敏感性表现为链霉菌>枯草芽胞杆菌>大肠杆菌>啤酒酵母菌,对微生物毒性顺序为Hg2+>Cd2+>Cr6+>Pb2+。     

绿航绿萝和金边吊兰对铅胁迫的生理响应

以绿航绿萝和金边吊兰为试验材料,测定Pb²⁺胁迫下植物叶片的生理生化变化,探讨绿航绿萝和金边吊兰对重金属胁迫的响应。结果表明,绿航绿萝可溶性糖含量随着铅处理时间的延长和铅处理浓度的升高表现为先升后降的趋势;游离脯氨酸、丙二醛、叶绿素含量总体上呈现升高趋势;可溶性蛋白含量则呈降低趋势。金边吊兰可溶性糖、游离脯氨酸、丙二醛含量随着铅处理时间的延长和铅处理浓度的升高表现为升高趋势;可溶性蛋白含量呈降低趋势;叶绿素含量总体上呈现先升后降的趋势。运用隶属函数法对绿航绿萝和金边吊兰抗重金属铅污染能力进行综合评判,结果表明, 金边吊兰优于绿航绿萝。     

RNA interference directs innate immunity against viruses in adult Drosophila

Innate immunity against bacterial and fungal pathogens is mediated by Toll and immune deficiency (Imd) pathways, but little is known about the antiviral response in Drosophila. Here, we demonstrate that an RNA interference pathway protects adult flies from infection by two evolutionarily diverse viruses. Our work also describes a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 act as host sensor and effector, respectively. These findings establish a Drosophila model for studying the innate immunity against viruses in animals.     

Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR

A large body of evidence indicates that metazoan innate immunity is regulated by the nervous system, but the mechanisms involved in the process and the biological importance of such control remain unclear. We show that a neural circuit involving npr-1, which encodes a G protein-coupled receptor (GPCR) related to mammalian neuropeptide Y receptors, functions to suppress innate immune responses. The immune inhibitory function requires a guanosine 3',5'-monophosphate-gated ion channel encoded by tax-2 and tax-4 as well as the soluble guanylate cyclase GCY-35. Furthermore, we show that npr-1- and gcy-35-expressing sensory neurons actively suppress immune responses of nonneuronal tissues. A full-genome microarray analysis on animals with altered neural function due to mutation in npr-1 shows an enrichment in genes that are markers of innate immune responses, including those regulated by a conserved PMK-1/p38 mitogen-activated protein kinase signaling pathway. These results present evidence that neurons directly control innate immunity in C. elegans, suggesting that GPCRs may participate in neural circuits that receive inputs from either pathogens or infected sites and integrate them to coordinate appropriate immune responses.