Pyogenic bacterial infections in humans with MyD88 deficiency

MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.     

Host resistance to lung infection mediated by major vault protein in epithelial cells

The airway epithelium plays an essential role in innate immunity to lung pathogens. Ribonucleoprotein particles primarily composed of major vault protein (MVP) are highly expressed in cells that encounter xenobiotics. However, a clear biologic function for MVP is not established. We report here that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, and maximal recruitment is dependent on bacterial binding to the cystic fibrosis transmembrane conductance regulator. MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa. These results suggest that MVP makes a substantial contribution to epithelial cell-mediated resistance to infection.     

小麦近缘种属对赤霉病菌的抗性评价

对来自不同国家和地区的小麦野生近缘植物７个属———山羊草属（Ａｅｇｉｌｏｐｓ）鹅观草属（Ｒｏｅｇｎｅｒｉ ａ）、大麦属（Ｈｏｒｄｅｕｍ）、赖草属（Ｌｅｙｍｕｓ）、冰草属（Ａｇｒｏｐｙｒｏｎ）、披碱草属（Ｅｌｙｍｕｓ）、和偃麦草属（Ｅｌｙｔｒｉｇｉａ）共３６个种的２０２份材料采用自然发病鉴定和人工接种鉴定方法,进行了抗赤霉病穗腐的鉴定。结果是：鹅观草属中有９个种的６１份材料具有高抗扩展特性,侵染仅限于小穗,不扩展至主穗轴,有部份材料同时还具有一定抗侵入能力;山羊草属有１份材料经接种鉴定具有一定抗侵入能力,该属的其余材料和其余５个属的材料均表现感病,既不抗侵入也不抗扩展。因此从鹅观草属的材料向小麦转移抗赤霉病基因是很有前途的。     

猪病混合感染对临床诊断的影响

[目的]寻求科学的解决猪病的混合感染问题。[方法]分析近几年猪病的流行特点,归纳出几种常见的混合感染,探讨混合感染对临床诊断的影响,分析其科学原理。[结果]应采取综合防制,包括:搞好科学的免疫工作;从各方面减少病原微生物积累与传播,尽量减少应激因子,增强猪体抵抗力等。[结论]该文为解决猪病的混合感染提供了理论基础。     

Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.     

Immunity and intracellular infection: resistance to bacteria in mice infected with a protozoan

Mice infected with the intracellular parasite Toxoplasma gondii for periods of as long as 7 months were resistant to challenge with numbers of Listeria monocytogenes and Salmonella typhimurium that were uniformly lethal to normal mice. This resistance did not appear to depend on the strain of toxoplasma employed or the route of inoculation of either toxoplasma or bacteria. Onset of immunity to listeria was demonstrable as early as 1 to 2 days after infection with toxoplasma. Resistance to toxoplasma was not demonstrable in mice immune to listeria. Interferon did not appear to be a mediator of the immunity observed in toxoplasma-infected mice.     

家畜抗病机理和抗病育种

疾病的发生给畜牧业造成了巨大的经济损失。疾病抗性通常由非特异性免疫和特异性免疫控制。除免疫基因外的非免疫基因对疾病的抗性也起很大作用。家畜疾病抗性是一种普遍现象，这种现象的本质，也就是疾病抗性是由基因控制的。这表明，对疾病抗性的选择有一个坚实基础。抗病育种是控制疾病的有效方法之一。     

CIMMYT高降雨量区小麦种质资源的农艺性状和抗性评价

为选择适应湖北省等高降雨量区小麦新品系或中间育种材料,对引进的16份国际玉米小麦改良中心(CIMMYT)高降雨量区小麦种质资源进行了生育期和简单农艺性状的调查,并对其中的9份种质进行了多抗性鉴定.结果表明,与湖北省大面积主栽品种郑麦9023相比,供试种质的拔节期平均提前4d,抽穗期推迟8 d,成熟期推迟1 d,成穗率、穗粒重和千粒重较低,株高和穗粒数较高;供试种质对条锈病的抗性最好,其次是赤霉病和白粉病,赤霉病抗侵染性比抗扩展性好.筛选出免疫或高抗条锈病种质7份;4份赤霉病抗侵染种质中有1份高抗侵染、中抗扩展;1份种质高抗白粉病,没有发现纹枯病抗性种质.     

中药合成制剂"免疫抗毒散"的药效试验

选用中药合成制剂"免疫抗毒散",通过对猪瘟的抗体效价增强试验、鸡胚攻毒试验、雏鸡人工发病试验、抑菌试验以及对小白鼠免疫器官的影响试验,验证了该中药制剂的药效作用.结果表明,"免疫抗毒散"能提高畜禽的抗体水平,具有杀灭病毒、保护胚胎的作用;能提高雏鸡的抗病能力,降低发病率和死亡率;对革兰氏阳性菌、革兰氏阴性菌均有较强的抑菌作用,其最小菌浓度为4mg·mL-1;并能促进小白鼠免疫器官的发育.     

家禽免疫抑制病的防治

家禽免疫抑制病可导致疫苗免疫失败、机体抗病力下降,从而引发多种病毒病及细菌的继发感染甚至死亡。防治免疫抑制性疾病,提高自身的免疫力成为防治家禽疾病的1条有效途径。鸡脾转移因子主要成分为低分子肽-核酸复合物,能有效增强机体免疫系统的发育,改善受损的免疫器官,提高机体的免疫力和抗病力。     

Pig macrophages with site-specific edited CD163 decrease the susceptibility to infection with porcine reproductive and respiratory syndrome virus

Porcine reproductive and respiratory syndrome (PRRS) is recognized as one of the most infectious viral diseases of swine. Although Cluster of differentiation 163 (CD163) is identified as an essential receptor for mediating PRRS virus (PRRSV) infection, the important residues involved in infection on CD163 are still unclear. Therefore, it is very important to identify these key residues to study the mechanism of PRRSV infection and to generate anti-PRRSV pigs. In this study, we first generated immortalized porcine alveolar macrophage (IPAM) cell lines harboring 40-residues (residues 523–562, including R561 (arginine (R) at position 561)) deletion of CD163. PRRSV infection experiments showed that these IPAM cell lines were completely resistant to PRRSV infection. We then generated cloned pigs carrying CD163-R561A (an arginine (R) to alanine (A) substitution at position 561 of CD163). PRRSV challenge experiments in porcine alveolar macrophages (PAMs) isolated from the CD163-R561A pigs showed significantly lower susceptibility to PRRSV than that of CD163-R561 PAMs. Through this study, we show that CD163 523–562 contains essential residues for mediating PRRSV infection, and that CD163 R561 significantly contributes to PRRSV infection but is not essential for infection. These functional sites can therefore serve as new targets for understanding the mechanism of PRRSV infection. Furthermore, CD163-R561A pigs can be used as an important model for improving pig germplasm with resistance against PRRSV.     

Immunity to schistosomes: progress toward vaccine

Among the major parasitic infections, schistosomiasis may be the most promising candidate for human vaccination. Information about mechanisms of immunity, gained mainly from experimental models but likely to be relevant to human infection, indicates a dynamic balance between protective and regulatory (blocking) mechanisms. Besides cell-mediated responses leading to macrophage activation, antibody-dependent cell-mediated cytotoxicity systems involving precise antibody isotypes and nonlymphoid cells (mononuclear phagocytes, eosinophils, and platelets) appear to be essential effectors of immune attack. The slow development of immunity in humans seems related to the production of antibodies that cross-react with schistosomulum surface antigen and block the binding of antibodies of the effector isotype. Schistosomes that survive in the bloodstream and produce chronic infections may evade the immune system as a result of intrinsic changes in membrane susceptibility and of transient expression of target antigens; at other stages of the parasite life cycle, cross-reactive molecules may be secreted that play an essential role in the induction of immunity. Several schistosome proteins have been characterized as candidates for vaccination. Among these, an antigen of 28 kilodaltons has been cloned and shown to be immunogenic in humans and protective in mice, rats, and baboons.     

Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells

The classical paradigm for dendritic cell function derives from the study of Langerhans cells, which predominate within skin epidermis. After an encounter with foreign agents, Langerhans cells are thought to migrate to draining lymph nodes, where they initiate T cell priming. Contrary to this, we show here that infection of murine epidermis by herpes simplex virus did not result in the priming of virus-specific cytotoxic T lymphocytes by Langerhans cells. Rather, the priming response required a distinct CD8alpha+ dendritic cell subset. Thus, the traditional view of Langerhans cells in epidermal immunity needs to be revisited to accommodate a requirement for other dendritic cells in this response.     

猪诺如病毒巢式RT-PCR检测方法的建立与应用

为了解中国猪群中猪诺如病毒感染情况,本研究根据猪诺如病毒保守的RNA依赖性RNA多聚酶(RNA Dependent RNA Polymerase,RDRP)基因序列设计了一套巢式RT-PCR引物,用该引物从猪粪便样品中扩增出与预期目的产物大小一致的条带,经克隆、测序后获得的序列与GenB ank数据库序列比对,证明所扩增的序列属于猪诺如病毒,表明本研究成功建立了猪诺如病毒巢式RT-PCR检测方法。该检测方法具有高特异性和敏感性,应用该方法检测某猪场健康育肥猪粪便样品,阳性率为54.5%。通过RDRP基因进行核苷酸同源比对发现本文获得的猪诺如病毒Wuning 1株属于GII群诺如病毒,与美国猪诺如病毒毒株OH-QW101/03/US、中国猪诺如病毒毒株Norovirus pig/GII/Ch6/China/2009核苷酸序列同源性最近。值得注意的是猪诺如病毒Wuning1毒株与武汉人诺如病毒毒株E2120/CHN/2010核苷酸同源性高达77.1%,说明猪诺如病毒Wuning 1毒株与武汉人诺如病毒基因组上亲缘性较近。本研究成功建立了一种检测猪诺如病毒的巢式RT-PCR方法,并应用于临床猪粪便样品的检测,为猪诺如病毒的诊断与监测提供了可供借鉴的方法、为猪诺如病毒的进化、分子病毒学及与人诺如病毒关系的深入研究提供依据。     

The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia

B cells can function as antigen-presenting cells and accessory cells for T cell responses. This study evaluated the role of B cells in the induction of protective T cell immunity to a Friend murine leukemia virus (F-MuLV)-induced leukemia (FBL). B cell-deficient mice exhibited significantly reduced tumor-specific CD4+ helper and CD8+ cytotoxic T cell responses after priming with FBL or a recombinant vaccinia virus containing F-MuLV antigens. Moreover, these mice had diminished T cell responses to the vaccinia viral antigens. Tumor-primed T cells transferred into B cell-deficient mice effectively eradicated disseminated FBL. Thus, B cells appear necessary for efficient priming but not expression of tumor and viral T cell immunity.     

Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity

Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus-type 1 (KOS strain)] and bacterial infection (Listeria monocytogenes) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-gamma production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.     

Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation

T helper 1 (TH1) cells mediate cellular immunity, whereas TH2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine TH1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative Rac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression.     

Restriction of an extinct retrovirus by the human TRIM5alpha antiviral protein

Primate genomes contain a large number of endogenous retroviruses and encode evolutionarily dynamic proteins that provide intrinsic immunity to retroviral infections. We report here the resurrection of the core protein of a 4-million-year-old endogenous virus from the chimpanzee genome and show that the human variant of the intrinsic immune protein TRIM5alpha can actively prevent infection by this virus. However, we suggest that selective changes that have occurred in the human lineage during the acquisition of resistance to this virus, and perhaps similar viruses, may have left our species more susceptible to infection by human immunodeficiency virus type 1 (HIV-1).