Single nucleotide polymorphisms in collagenous lectins and other innate immune genes in pigs with common infectious diseases

Innate immune recognition of pathogens involves various surface receptors and soluble proteins that precede agglutination, complement activation, phagocytosis, and the adaptive immune response. Mannan-binding lectins (MBLs), ficolins (FCNs) and surfactant protein A (SP-A) are soluble collagenous lectins that bind surface structures of various bacteria, viruses and fungi. Some single nucleotide polymorphisms (SNPs) in collagenous lectin genes of humans and other species, including pigs, have been implicated in variation in susceptibility to infectious and inflammatory diseases. In this study we determined the frequencies of 13 SNP alleles of MBL-A, MBL-C, ficolin-α, ficolin-β, and SP-A in 1324 healthy pigs and 461 pigs diagnosed with common infectious diseases at necropsy. For comparison, we also analyzed 12 other SNP alleles in several other innate immune genes, including galectins and TLRs. Several SNPs within genes encoding porcine MBL-A, MBL-C and SP-A were more frequent in pigs diagnosed at necropsy with various diseases or pathogens. These findings suggest that several collagenous lectin SNPs are associated with disease susceptibility and therefore might be genetic markers of impaired innate immune function.     

精氨酸对动物免疫功能影响研究进展

精氨酸对畜禽来说是一种重要的氨基酸,它参与体内多种营养物质的合成与代谢。同时它又可作为一种免疫调节剂。本文就精氨酸对动物免疫功能的影响作一综述,并阐述了精氨酸影响免疫功能的机理,以期对今后精氨酸的研究提供参考。     

肽聚糖在天然免疫中的作用研究

肽聚糖是细菌等原核生物细胞壁的特有成分,但它在天然免疫系统中的作用长期被低估。近年来的研究资料表明,肽聚糖识别蛋白是一类与肽聚糖结合的模式识别受体,可识别入侵细菌,激活相应的免疫反应,在免疫应答中发挥重要作用。随着对免疫机制研究的进一步深入,肽聚糖在医学、畜牧和生物工程等领域中的应用将会有更广阔的前景。     

日粮中多不饱和脂肪酸对动物免疫功能影响的研究

随着人民生活水平的提高，人们对安全、绿色食品的需求量越来越多。而磺胺类和抗生素类药物在动物生产中的应用非常广泛，随之带来的就是因药物残留引起一系列的食品安全问题。在日粮中添加多不饱和脂肪酸（PUFA）可以提高动物的免疫功能，从而减少动物患病的可能及动物生产过程中用药的机会。因此，多不饱和脂肪酸的应用可以为安全食品的提供做出贡献。本文对PuFA对动物免疫功能的影响作一综述。     

In vivo priming heterophil innate immune functions and increasing resistance to Salmonella enteritidis infection in neonatal chickens by immune stimulatory CpG oligodeoxynucleotides

Oligodeoxynucleotides (ODN) containing CpG dinucleotides (CpG-ODN) mimic bacterial DNA and stimulate the innate immune system of vertebrates. Here, we investigated the effects of intraperitoneal (ip) administered CpG-ODN on the innate immune functions of chicken heterophils. Our results demonstrated CpG-ODN-dependent priming of chicken heterophil degranulation and oxidative burst. Heterophils from chickens treated with CpG-ODN exhibited significantly higher (p<0.05) degranulation activity compared to PBS and control ODN (ODN containing no CpG motif) treated groups when stimulated with opsonized Salmonella enterica serovar enteritidis. Similarly, oxidative burst activity, which generates bactericidal reactive oxygen species, was significantly higher (p<0.05) in heterophils from the CpG-ODN treated group than from PBS and control ODN groups when stimulated with formalin-killed S. enteritidis. The priming effects of CpG-ODN on heterophil immune functions continued at least 4 days post-treatment. In the infection study, newly hatched chickens were treated with CpG-ODN, control ODN or PBS for 24h then challenged with oral inoculation of S. enteritidis. A significant reduction (p<0.05) in colonization by S. enteritidis was observed in chickens treated with CpG-ODN. Our study provides evidence that immunostimulatory CpG-ODN potentiates the innate immune responses of heterophils and enhances resistance to infectious pathogens in neonatal chickens.     

Evaluation of innate immune responses in bovine forestomachs

Previous studies had indicated an active role of bovine forestomachs in the response to alimentary disorders as well as to inflammatory and infectious processes in both the gastro-intestinal (GI) tract and elsewhere. We investigated the potential of bovine forestomachs to receive, elaborate and produce signals and mediators of the innate immune response. Indeed, we detected the expression of Toll IL-1R8/single Ig IL-1-related receptor (TIR8/SIGIRR) and other receptors and cytokines, such as Toll-like receptor (TLR)4, interleukin (IL)-1β, IL-10 and Caspase-1 in the forestomach walls of healthy cows. Their presence suggests an active role of forestomachs in inflammatory disorders of the GI tract and other body compartments. Moreover, interferon (IFN)-γ was revealed in ruminal content. We confirmed and further characterized the presence of leukocytes in the rumen fluids. In particular, T-, B-lymphocytes and myeloid lineage cells were detected in the ruminal content of both rumen-fistulated heifers and diseased cows. An acidogenic diet based on daily supplements of maize was shown to inhibit leukocyte accumulation, as opposed to a control, hay-based diet, with or without a soy flour (protein) supplement. On the whole, results indicate that bovine forestomachs can receive and elaborate signals for the immune cells infiltrating the rumen content or other organs. Forestomachs can thus participate in a cross-talk with the lymphoid tissues in the oral cavity and promote regulatory actions at both regional and systemic levels; these might include the control of dry matter intake as a function of fundamental metabolic requirements of ruminants.     

水产动物营养与免疫

水产动物营养与免疫有密切的关系,饵料中营养不足或不平衡都可能对免疫功能产生不利的影响,而水产动物的健康状况又反过来影响营养素的需求量。近年来,许多学者从营养免疫学角度对水产动物的免疫功能及抗病能力进行了大量的研究。     

The innate immune response against Brucella in humans

Pathogens have developed different strategies to survive and multiply within their host. Among them is the ability to control phagocyte apoptosis while another is to affect the expression of cytokines which is necessary for a normal protective function of the immune response. To establish themselves and cause chronic disease in humans and animals, Brucella spp. invade and proliferate within monocytic phagocytes. We have established that in humans, Brucella suis impairs the apoptosis of monocytes and macrophages, thus preventing its host cell elimination. In mice, which are not naturally colonized by the bacteria, Brucella infection results in Type1 (Th1) cellular immune response which promotes a clearance of the bacterial organism. The development of this response is under the control of major cytokines like TNF-alpha, IFN-gamma and IL-12 produced at the onset of infection. We have observed that in humans, B. suis-infected macrophages which produce IL-1, IL-6, IL-10 and several chemokines including IL-8, do not secrete TNF-alpha. By constructing null mutants, we demonstrated that this inhibition involves the outer membrane protein Omp25 of Brucella, however the mechanism regulating the inhibition has not yet been clearly defined. It is likely that the Omp25-induced effect on TNF-alpha production assists bacterial evasion of antimicrobial defences at different levels. Firstly, by preventing the autocrine activation of macrophages thus inhibiting innate immunity and secondly by impairing the production of IL-12 and the development of a Th1 type specific immunity. In addition to the central role of the macrophage in Brucella infection, others cells of the innate immune response are recruited and influenced by the interactions between bacteria and host. For instance, human Vgamma9Vdelta2 T-cells play an important role in the early response to infection with intracellular pathogens. Evidence has been presented that their number dramatically increased in the peripheral blood of patients with acute brucellosis. We have shown that human Vgamma9Vdelta2 T-cells can be specifically activated by non-peptidic low molecular weight compound(s) from B. suis lysate or by soluble factors produced by B. suis-infected macrophages. Under these conditions, they produce TNF-alpha and IFN-gamma and reduce the bacterial multiplication inside infected autologous macrophages. This impairment of B. suis multiplication is due to both soluble factors released from activated gammadeltaT-cells (including TNF-alpha and IFN-gamma) and to a contact-dependent cytotoxicity directed against the infected cells. The interactions between the bacteria and these cells can counteract the intramacrophagic development of the bacteria and finally influence the further development of the host defense. We hypothesize that the chronicity or the elimination of the infection will depend on the balance between contradictory effects induced by the bacteria which favor either the host or the pathogen. Moreover, the interrelationship between the different cells must be taken into account in the analysis of the virulence of the bacteria and in the development of in vitro models of human macrophage infection.     

TOLL-like receptors linking innate and adaptive immune response

Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, which is mediated by B and T lymphocytes, recognises pathogens by rearranged high affinity receptors. However, the establishment of adaptive immunity is often not rapid enough to eradicate microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defense mechanisms are provided by innate immunity, which recognises invading pathogens by germ-line-encoded pattern recognition receptors (PRR). Recent evidence shows that this recognition can mainly be attributed to the family of TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns (PAMP) to TLR induces the production of reactive oxygen and nitrogen intermediates (ROI and RNI), pro-inflammatory cytokines, and up-regulates expression of co-stimulatory molecules, subsequently initiating the adaptive immunity. In this review, we will summarize the discovery and the critical roles of the TLR family in host defense, briefly allude to signaling mechanisms mediating the response to TLR ligands, and will provide an update on current knowledge regarding the ligand specificity of these receptors and their role in immunity of domestic animals, particularly cattle.     

Passive and active components of neonatal innate immune defenses

Innate immune defenses are crucial for survival in the first days and weeks of life. At birth, newborns are confronted with a vast array of potentially pathogenic microorganisms that were not encountered in utero. At this age, cellular components of the adaptive immune system are in a naive state and are slow to respond. Antibodies received from the dam are essential for defense, but represent a finite and dwindling resource. Innate components of the immune system detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and their products) by means of pattern-recognition receptors (PRRs). Soluble mediators of the innate system such as complement proteins, pentraxins, collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to structures on pathogens, leading to agglutination, interference with receptor binding, opsonization, neutralization, direct membrane damage and recruitment of additional soluble and cellular elements through inflammation. Cell-associated receptors such as the Toll-like receptors (TLRs) can activate cells and coordinate responses (both innate and adaptive). In this paper, accumulated knowledge of the receptors, soluble and cellular elements that contribute to innate defenses of young animals is reviewed. Research interest in this area has been intermittent, and the literature varies in quantity and quality. It is hoped that documentation of the limitations of our knowledge base will lead to more extensive and enlightening studies.     

不同品种绵羊和山羊主要先天性免疫指标的比较

对4个山羊品种和4个绵羊品种的7项主要先天性免疫学指标进行了检测并比较。对动物进行颈静脉采血,制备血清,用ELISA试剂盒测定IL-1、IL-2、IL-6、IL-18、IFN-γ、NK细胞、血清溶菌酶。利用生物统计学的方法和原理,以品种和品种来源地为应变量对检测结果进行比较分析。结果表明,山羊当地品种的NK和LYS高于引进品种（P〈0.05）;绵羊引进品种的IL-1、IL-2、IL-6、IL-18、IFN-γ、NK、LYS均明显高于地方品种（P〈0.01）。在不同品种之间,莱芜黑山羊NK和LYS水平高于崂山奶山羊、波尔山羊和鲁波山羊,萨福克羊的IL-1、IL-6、IL-18、IFN-γ、LYS水平最高且差异极显著（P〈0.01）。小尾寒羊IL-18、IFN-γ水平最低且差异极显著（P〈0.01）。说明不同种群绵羊、山羊的先天性免疫水平存在显著差异,为以后抗病育种提供合理的试验数据。     

Viral deubiquitinases and innate antiviral immune response in livestock and poultry

Among many of the pathogens, virus is the main cause of diseases in livestock and poultry. A host infected with the virus triggers a series of innate and adaptive immunity. The realization of innate immune responses involves the participation of a series of protein molecules in host cells, including receptors, signal molecules and antiviral molecules. Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular or viral deubiquitinases (DUBs). DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. In this review, we briefly introduce the mechanisms of ubiquitination and deubiquitination, present antiviral innate immune response and its regulation by ubiquitin, and summarize the prevalence of DUBs encoded by viruses (Arteriviridae, Asfarviridae, Nairoviridae, Coronaviridae, Herpesviridae, and Picornaviridae) infecting domestic animals and poultry. It is found that these DUBs suppress the innate immune responses mainly by affecting the production of type I interferon (IFN), which causes immune evasion of the viruses and promotes their replication. These findings have important reference significance for understanding the virulence and immune evasion mechanisms of the relevant viruses, and thus for the development of more effective prevention and treatment measures.     

Functional polymorphisms in Toll-like receptor genes for innate immunity in farm animals

The exploitation of the genetic factors affecting the health status of farm animals represents an alternative approach to controlling the diseases caused by microbial pathogens. The determination of innate immunity based on the genotype of the germplasm cells is a constraint for specificity but becomes an advantage in breeding schemes. The structural deviations among Toll-like receptors (TLRs), as the most frequently studied innate immunity components, have been documented at all levels, i.e., interspecific, inter- and intravarietal, in the main farm species. The current computational methods facilitate the prediction of the functional consequences of the observed mutations. Subsequently, these predictions can be verified through immunological responsiveness and population-wide association studies. The frequency and haplotype grouping of individual polymorphisms are used to track the origin and selection coefficient as independent indicators of functional changes. The Toll-like receptor variants associated with mastitis and mycobacterial infection have been identified in cattle, consequently, the targeting of these proteins in breeding could contribute to disease control. The range of infections affected by TLR polymorphisms suggests that the improvement of innate resistance is feasible in more species. Thus, the traditional breeds and wild populations should be regarded as the resources of genetic variability accessible for these purposes.     

Comparative pathology of glomerulonephritis in animals.

Glomerulonephritis constitutes an important category of renal diseases in animals and has been recognized with increasing frequency in the last decade. We report here the comparative morphologic aspects of glomerulonephritis as a naturally occurring disease of animals. We briefly review the immunopathogenesis of glomerulonephritis. The morphology of renal lesions occurring in glomerulonephritis in dogs, cats, cattle, sheep, horses and swine has been reviewed with emphasis on the range and specificity of various glomerular lesions and on the comparison of lesions between various species. A distinction was made between glomerulonephritis as a primary disease entity and glomerulonephritis associated with other disease processes. Primary idiopathic glomerulonephritis occurred in all species but was most commonly recognized as a clinically important disease in dogs and cats. Glomerulonephritis also occurred in association with other diseases such as equine infectious anemia, chronic hog cholera, canine pyometra, dirofilariasis, feline leukemia virus infection and canine systemic lupus erythematosus.     

寡糖对动物免疫功能的作用

寡糖（oligosaccharides）又称为低聚糖或寡聚糖，是由2～10个单糖单位通过糖苷键连接而成的小聚合体，介于单体单糖与高度聚合的多糖之间。寡糖是中等分子的非淀粉多糖，大分子非淀粉多糖经相应酶的不完全水解可产生寡糖。在饲料中使用适量的寡糖，可以提高动物的生产性能，改善动物的健康状况，提高免疫力，防止腹泻。大量研究表明，寡糖除能改善动物消化道微生物区系，促进消化道有益菌的生长，抑制有害微生物的繁殖外，还具有调节动物机体免疫反应，     

Comparative toxicology of monensin sodium in laboratory animals

The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)