Antimicrobial peptides in the interactions between insects and flagellate parasites

Innate immunity has a key role in the control of microbial infections in both vertebrates and invertebrates. In insects, including vectors that transmit parasites that cause major human and animal diseases, antimicrobial peptides (AMPs) are important components of innate immunity. AMPs are induced upon parasitic infections and can participate in regulating parasite development in the digestive tract and in the hemolymph. This review presents our current knowledge of a field that is in its infancy: the role of innate immunity in different models of insects infected with flagellate parasites, and in particular the potential role of AMPs in regulating these parasitic infections.     

Biological characterization and modes of action of temporins and bombinins H, multiple forms of short and mildly cationic anti-microbial peptides from amphibian skin.

Genetically encoded cationic anti-microbial peptides (AMPs) are essential components of the ancient and non-specific innate immune system, which is the principal defence mechanism of all species of life, with the primary role to kill infectious microorganisms. Amphibian skin is one of the richest natural sources of such molecules, which are produced by holocrine-type dermal glands and released upon stimulation. This review highlights the attractive and unique structural/functional properties of temporins and bombinins H, two families of short and mildly cationic peptides, isolated from the skin of frogs belonging to Rana and Bombina genera, respectively. Beside improving our knowledge on the role of AMPs in the regulation of the innate immunity, the biological significance of the existence of multiple forms of a prototypic peptide sequence within the same organism and the implication of short peptides in the endotoxin neutralization, these two classes of AMPs can be also considered as valid candidates for the design of novel anti-infective and anti-sepsis drugs.     

Biotic stress resistance in agriculture through antimicrobial peptides

Antimicrobial peptides (AMPs) are the hosts' defense molecules against microbial pathogens and gaining extensive research attention worldwide. These have been reported to play vital role of host innate immunity in response to microbial challenges. AMPs can be used as a natural antibiotic as an alternative of their chemical counterpart for protection of plants/animals against diseases. There are a number of sources of AMPs including prokaryotic and eukaryotic organisms and are present, both in vertebrates and invertebrates. AMPs can be classified as cationic or anionic, based on net charges. Large number of databases and tools are available in the public domain which can be used for development of new genetically modified disease resistant varieties/breeds for agricultural production. The results of the biotechnological research as well as genetic engineering related to AMPs have shown high potential for reduction of economic losses of agricultural produce due to pathogens. In this article, an attempt has been made to introduce the role of AMPs in relation to plants and animals. Their functional and structural characteristics have been described in terms of its role in agriculture. Different sources of AMPs and importance of these sources has been reviewed in terms of its availability. This article also reviews the bioinformatics resources including different database tools and algorithms available in public domain. References of promising biotechnology research in relation to AMPs, prospects of AMPs for further development of genetically modified varieties/breeds are highlighted. AMPs are valuable resource for students, researchers, educators and medical and industrial personnel.     

果蝇抗微生物肽基因的免疫诱导模式

果蝇作为一种模式昆虫,为研究昆虫和人类的先天免疫发挥了重要作用。目前对果蝇体内免疫诱导产生的抗微生物肽多基因家族在分子进化、抗菌功能的分子特征和免疫诱导表达的信号传递机制等方面的研究进展,进一步加深了人们对昆虫乃至其他动物和人类先天免疫模式的认识,为研究其他昆虫特别是作为主要农林害虫的鳞翅目昆虫的先天免疫机制发挥了重要作用。本文集中对黑腹果蝇Drosophila melanogaster抗微生物肽及其免疫模式的研究结果和最新进展进行了介绍,其中包括作者近几年的研究结果。     

Antimicrobial peptides and proteins, exercise and innate mucosal immunity

This review examines the question of whether exercise can be used as an experimental model to further our understanding of innate antimicrobial peptides and proteins (AMPs) and their role in susceptibility to infection at mucosal surfaces. There is strong evidence to suggest that AMPs, in combination with cellular and physical factors, play an important role in preventing infection. Although AMPs act directly on microorganisms, there is increasing recognition that they also exert their protective effect via immunomodulatory mechanisms, especially in noninflammatory conditions. Further studies that manipulate physiologically relevant concentrations of AMPs are required to shed light on the role they play in reducing susceptibility to infection. Evidence shows that in various form prolonged and/or exhaustive exercise is a potent modulator of the immune system, which can either sharpen or blunt the immune response to pathogens. The intensity and duration of exercise can be readily controlled in experimental settings to manipulate the degree of physical stress. This would allow for an investigation into a potential dose-response effect between exercise and AMPs. In addition, the use of controlled exercise could provide an experimental model by which to examine whether changes in the concentration of AMPs alters susceptibility to illness.     

Life is a huge compromise: Is the complexity of the vertebrate immune-neuroendocrine system an advantage or the price to pay?

Recent advances in comparative immunology have established that invertebrates produce hypervariable molecules probably related to immunity, suggesting the possibility of raising a specific immune response. “Priming” and “tailoring” are terms now often associated with the invertebrate innate immunity. Comparative immunologists contributed to eliminate the idea of a static immune system in invertebrates, making necessary to re-consider the evolutive meaning of immunological memory of vertebrates. If the anticipatory immune system represents a maximally efficient immune system, why can it be observed only in vertebrates, especially in consideration that molecular hypervariability exists also in invertebrates? Using well-established theories concerning the evolution of the vertebrate immunity as theoretical basis we analyze from an Eco-immunology-based perspective why a memory-based immune system may have represented an evolutive advantage for jawed vertebrates. We hypothesize that for cold-blooded vertebrates memory represents a complimentary component that flanks the robust and fundamental innate immunity. Conversely, immunological memory has become indispensable and fully exploited in warm-blooded vertebrates, due to their stable inner environment and high metabolic rate, respectively.     

脂多糖诱导的水椰八角铁甲免疫响应动态及其在性别间的差异

【目的】研究昆虫免疫诱导后的响应模式是揭示昆虫免疫适应性变异、免疫权衡和免疫致敏现象的关键。本研究旨在探讨水椰八角铁甲 Octodonta nipae (Maulik)免疫诱导的动态响应变化及其在性别间的差异。【方法】将革兰氏阴性细菌细胞壁提取物脂多糖（LPS）注射到水椰八角铁甲雌雄成虫体腔内,诱导其免疫系统响应,测定了两个重要免疫参数酚氧化酶（phenoloxidase, PO）活性和抗菌肽（antimicrobial peptide, AMP）抑菌活性在免疫诱导前后的动态变化。【结果】LPS（2.5 mg/mL×138 nL）诱导可以使水椰八角铁甲PO活性和AMPs的抑菌活性在一定时间范围内（雌虫PO活性和AMPs抑菌活性分别在诱导后4-10 h和12-48 h,雄虫PO活性和AMPs抑菌活性分别在诱导后0.1-10 h和4-48 h）显著高于空白对照;AMPs抑菌活性的提升时间迟于PO活性。但持续时间长于PO活性。免疫诱导前,成虫的PO活性和AMPs抑菌活性均是雌性显著高于雄虫;同样在免疫诱导后,成虫PO活性和AMPs抑菌活性的最高水平也是雌性显著大于雄虫,但活性提升的时间是雄性早于雌虫。【结论】LPS能够显著诱导水椰八角铁甲雌雄成虫的免疫响应,而且雌成虫的免疫响应明显高于雄性。通过对水椰八角铁甲免疫物质动态变化的认识,为水椰八角铁甲入侵到新生境后免疫相关适应性变异及安全有效的生物防治方法的研究奠定了基础。     

无脊椎动物清道夫受体的免疫调控

在长期进化的过程中,无脊椎动物逐渐形成了受体识别-信号传导-免疫应答为特征的天然免疫体系,以清除凋亡细胞或外界的病原微生物。清道夫受体（SRs）是一类位于细胞表面的跨膜受体,也是一类参与无脊椎动物天然免疫反应的重要模式识别受体。清道夫受体参与免疫反应的异己靶标识别,通过下游信号级联调控抗菌肽合成和吞噬作用。本文综述了无脊椎动物清道夫受体的种类、结构及其参与天然免疫的调控机制,探讨了无脊椎动物清道夫受体研究中尚待解决的问题。     

The evolution and genetics of innate immunity

The immune system provides protection from a wide range of pathogens. One component of immunity, the phylogenetically ancient innate immune response, fights infections from the moment of first contact and is the fundamental defensive weapon of multicellular organisms. The Toll family of receptors has a crucial role in immune defence. Studies in fruitflies and in mammals reveal that the defensive strategies of invertebrates and vertebrates are highly conserved at the molecular level, which raises the exciting prospects of an increased understanding of innate immunity.     

Strain-specific priming of resistance in the red flour beetle, Tribolium castaneum

As invertebrates lack the molecular machinery employed by the vertebrate adaptive immune system, it was thought that they consequently lack the ability to produce lasting and specific immunity. However, in recent years, it has been demonstrated that the immune defence of invertebrates is by far more complicated and specific than previously envisioned. Lasting immunity following an initial exposure that proves protection on a secondary exposure has been shown in several species of invertebrates. This phenomenon has become known as immune priming. In the cases where it is explicitly tested, this priming can also be highly specific. In this study, we used survival assays to test for specific priming of resistance in the red flour beetle, Tribolium castaneum, using bacteria of different degrees of relatedness. Our results suggest an unexpected degree of specificity that even allows for differentiation between different strains of the same bacterium. However, our findings also demonstrate that specific priming of resistance in insects may not be ubiquitous across all bacteria.     

Complement-Related Proteins Control the Flavivirus Infection of Aedes aegypti by Inducing Antimicrobial Peptides

The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)-containing proteins (TEPs), which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR), belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.     

Lipopolysaccharide (Endotoxin)-host defense antibacterial peptides interactions: Role in bacterial resistance and prevention of sepsis

Lipopolysaccharide (LPS) is the major molecular component of the outer membrane of Gram-negative bacteria and serves as a physical barrier providing the bacteria protection from its surroundings. LPS is also recognized by the immune system as a marker for the detection of bacterial pathogen invasion, responsible for the development of inflammatory response, and in extreme cases to endotoxic shock. Because of these functions, the interaction of LPS with LPS binding molecules attracts great attention. One example of such molecules are antimicrobial peptides (AMPs). These are large repertoire of gene-encoded peptides produced by living organisms of all types, which serve as part of the innate immunity protecting them from pathogen invasion. AMPs are known to interact with LPS with high affinities. The biophysical properties of AMPs and their mode of interaction with LPS determine their biological function, susceptibility of bacteria to them, as well as the ability of LPS to activate the immune system. This review will discuss recent studies on the molecular mechanisms underlying these interactions, their effects on the resistance of the bacteria to AMPs, as well as their potential to neutralize LPS-induced endotoxic shock.     

水生无脊椎动物中的免疫球蛋白超家族

适应性免疫一直被认为是脊椎动物特有的免疫机制,然而近年来许多研究表明 ,无脊椎动物体内也存在许多在结构或功能上与脊椎动物适应性免疫分子类似的免 疫成分. 免疫球蛋白超家族是适应性免疫的重要组成部分,本文主要综述近年来关 于水生无脊椎动物中肌联蛋白、唐氏综合症细胞黏着分子、特异性凝集素、几丁质 结合蛋白和185/133基因家族以及含有V和C结构域的蛋白等免疫球蛋白超家族成员研 究进展,这有助于深入理解无脊椎动物的免疫系统并揭示脊椎动物适应性免疫起源 与进化.     

Lipopolysaccharide (Endotoxin)-host defense antibacterial peptides interactions: role in bacterial resistance and prevention of sepsis

Lipopolysaccharide (LPS) is the major molecular component of the outer membrane of Gram-negative bacteria and serves as a physical barrier providing the bacteria protection from its surroundings. LPS is also recognized by the immune system as a marker for the detection of bacterial pathogen invasion, responsible for the development of inflammatory response, and in extreme cases to endotoxic shock. Because of these functions, the interaction of LPS with LPS binding molecules attracts great attention. One example of such molecules are antimicrobial peptides (AMPs). These are large repertoire of gene-encoded peptides produced by living organisms of all types, which serve as part of the innate immunity protecting them from pathogen invasion. AMPs are known to interact with LPS with high affinities. The biophysical properties of AMPs and their mode of interaction with LPS determine their biological function, susceptibility of bacteria to them, as well as the ability of LPS to activate the immune system. This review will discuss recent studies on the molecular mechanisms underlying these interactions, their effects on the resistance of the bacteria to AMPs, as well as their potential to neutralize LPS-induced endotoxic shock.     

昆虫抗菌肽结构、性质和基因调控

昆虫抗菌肽是昆虫先天免疫系统中非常重要的一类效应分子。昆虫抗菌肽带正电荷,分子量小,大多数少于100个氨基酸残基。根据结构可以将昆虫抗菌肽分为一些不同的家族。昆虫抗菌肽不同的抗菌谱表明,它具有不同的作用机制。以果蝇为模式生物研究表明,昆虫抗菌肽的基因调控涉及到多个信号通路及大量的信号分子。     

Molecular Characterization of Antimicrobial Peptide Genes of the Carpenter Ant Camponotus floridanus

The production of antimicrobial peptides (AMPs) is a major defense mechanism against pathogen infestation and of particular importance for insects relying exclusively on an innate immune system. Here, we report on the characterization of three AMPs from the carpenter ant Camponotus floridanus. Due to sequence similarities and amino acid composition these peptides can be classified into the cysteine-rich (e.g. defensin) and glycine-rich (e.g. hymenoptaecin) AMP groups, respectively. The gene and cDNA sequences of these AMPs were established and their expression was shown to be induced by microbial challenge. We characterized two different defensin genes. The defensin-2 gene has a single intron, whereas the defensin-1 gene has two introns. The deduced amino acid sequence of the C. floridanus defensins is very similar to other known ant defensins with the exception of a short C-terminal extension of defensin-1. The hymenoptaecin gene has a single intron and a very peculiar domain structure. The corresponding precursor protein consists of a signal- and a pro-sequence followed by a hymenoptaecin-like domain and six directly repeated hymenoptaecin domains. Each of the hymenoptaecin domains is flanked by an EAEP-spacer sequence and a RR-site known to be a proteolytic processing site. Thus, proteolytic processing of the multipeptide precursor may generate several mature AMPs leading to an amplification of the immune response. Bioinformatical analyses revealed the presence of hymenoptaecin genes with similar multipeptide precursor structure in genomes of other ant species suggesting an evolutionary conserved important role of this gene in ant immunity.