Two arms are better than one: parasite variation leads to combined inducible and constitutive innate immune responses

Parasites represent a major threat to all organisms which has led to the evolution of an array of complex and effective defence mechanisms. Common to both vertebrates and invertebrates are innate immune mechanisms that can be either constitutively expressed or induced on exposure to infection. In nature, we find that a combination of both induced and constitutive responses are employed by vertebrates, invertebrates and, to an extent, plants when they are exposed to a parasite. Here we use a simple within-host model motivated by the insect immune system, consisting of both constitutive and induced responses, to address the question of why both types of response are maintained so ubiquitously. Generally, induced responses are thought to be advantageous because they are only used when required but are too costly to maintain constantly, while constitutive responses are advantageous because they are always ready to act. However, using a simple cost function but with no a priori assumptions about relative costs, we show that variability in parasite growth rates selects for a strategy that combines both constitutive and induced defences. Differential costs are therefore not necessary to explain the adoption of both forms of defence. Clearly, hosts are likely to be challenged by variable parasites in nature and this is sufficient to explain why it is optimal to deploy both arms of the innate immune system.     

Extraction of intraerythrocytic malarial parasites by phagocytic cells

Phagocytosis is an intricate process adopted by some unicellular organisms as a feeding behaviour. It has developed in the tissues of multicellular organisms, both vertebrates and invertebrates, as a defence system to confine and eliminate foreign matter and, in this manner, protect the host against infection. During evolutionary development, phagocytic cells have evolved to show greater specificity. Lakshmi Kumaratilake, Antonio Ferrante, Jaliya Kumaratilake and Anthony Allison here describe a unique mechanism used by phogocytic leukocytes to engulf intra-erythrocytic malarial parasites.     

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.     

Transgenerational priming of immunity: maternal exposure to a bacterial antigen enhances offspring humoral immunity

Young vertebrates have limited capacity to synthesize antibodies and are dependent on the protection of maternally transmitted antibodies for humoral disease resistance early in life. However, mothers may enhance fitness by priming their offspring's immune systems to elevate disease resistance. Transgenerational induced defences have been documented in plants and invertebrates, but maternal priming of offspring immunity in vertebrates has been essentially neglected. To test the ability of mothers to stimulate the immune systems of offspring, we manipulated maternal and offspring antigen exposure in a wild population of birds, pied flycatchers (Ficedula hypoleuca). We show that immunization of the mother before egg laying apparently stimulates a transgenerational defence against pathogens by elevating endogenous offspring antibody production. If the disease environments encountered by mothers and offspring are similar, this transgenerational immune priming may allow young to better cope with the local pathogen fauna.     

环境污染对几类水生无脊椎动物内分泌功能扰乱的研究现状

近年来，在环境毒理学这门边缘学科中又诞生了一个新的领域，即环境污染对内分泌功能的扰乱。研究发现，许多人工合成的杀虫剂和工业化合物能够扰乱脊椎动物的内分泌功能，这些化合物也存在于水环境中。近年来，这些环境有机污染物是否对水生无脊椎动物的内分泌功能同样具有扰乱作用成了环境内分泌学这个新领域的热点之一。由于近年来的研究侧重于腔肠动物、轮虫、软体动物、甲壳动物及棘皮动物，因此，本文主要介绍有关环境污染物对这几类水生无脊椎动物内分泌功能扰乱的研究进展。另外，对环境污染对水生无脊椎动物内分泌扰乱这个研究热点的现状以及今后的发展方向进行了评述。在从事环境污染对无脊椎动物内分泌功能影响的研究时，研究者必须意识到无脊椎动物和脊椎动物在内分泌机制上的差异，不可随意地在这两大类动物类群之间互相引伸研究结果。     

The role of lectins in plant defence

Summary Recent progress in the search for the physiological role of plant lectins supports the idea that some of these proteins are involved in the defence mechanisms of the plant. To place the evidence in favour of such a defensive role in a broad perspective, a short overview is given of the most important plant pathogens and predators. In addition, the solutions that plants have developed to resist the continuous threat of a hostile environment are briefly discussed in relation to the protective role of proteins in general. The presumed involvement of plant lectins in defence mechanisms is first inferred from an analysis of the biochemical, physiological, cellular biological and molecular biological properties of plant lectins. Subsequently, the available experimental evidence for the involvement of lectins in the plant's defence against viruses, bacteria, fungi and herbivorous invertebrates and vertebrates is discussed in some detail. Since the defensive role of plant lectins is determined largely by their ability to recognize and bind foreign glycans, a brief discussion is given of how the basically protective properties of these proteins can be exploited for histochemical applications in biological and biomedical research.     

Inactivation of the type I interferon pathway reveals long double‐stranded RNA‐mediated RNA interference in mammalian cells

RNA interference (RNAi) elicited by long double‐stranded (ds) or base‐paired viral RNA constitutes the major mechanism of antiviral defence in plants and invertebrates. In contrast, it is controversial whether it acts in chordates. Rather, in vertebrates, viral RNAs induce a distinct defence system known as the interferon (IFN) response. Here, we tested the possibility that the IFN response masks or inhibits antiviral RNAi in mammalian cells. Consistent with that notion, we find that sequence‐specific gene silencing can be triggered by long dsRNAs in differentiated mouse cells rendered deficient in components of the IFN pathway. This unveiled response is dependent on the canonical RNAi machinery and is lost upon treatment of IFN‐responsive cells with type I IFN. Notably, transfection with long dsRNA specifically vaccinates IFN‐deficient cells against infection with viruses bearing a homologous sequence. Thus, our data reveal that RNAi constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.     

Nitric oxide synthase in invertebrates

Summary The gas nitric oxide is now recognized as an important signalling molecule that is synthesized froml-arginine by the enzyme nitric oxide synthase. This enzyme can be localized by different methods, including immunocytochemistry and the histochemical reaction for NADPH diaphorase. It has been demonstrated in various vertebrate cells and tissues, and recently several studies dealing with the production of nitric oxide in invertebrates have been published. Diploblastic animals, flatworms and nematodes seem to lack NADPH diaphorase activity but it has been found in the rest of the phyla studied. The most frequently reported sites for the production of nitric oxide are the central and peripheral nervous systems and, in primitive molluscs, the muscle cells. In insects, it has also been described in the Malpighian tubules. The roles of nitric oxide in invertebrates are closely related to the physiological actions described in vertebrates, namely, neurotransmission, defence, and salt and water balance. The recent cloning of the first nitric oxide synthase from an invertebrate source could open interesting avenues for further studies.     

Invertebrates as animal models for Staphylococcus aureus pathogenesis: a window into host-pathogen interaction

Recently, the use of invertebrate models of infection has given exciting insights into host-pathogen interaction for a number of bacteria. In particular, this has revealed important factors of the host response with remarkable parallels in higher organisms. Here, we review the advances attained in the elucidation of virulence determinants of a major human pathogen, Staphylococcus aureus, in relation to the invertebrate models thus far applied, the silkworm (Bombyx mori), the fruit fly (Drosophila melanogaster) and the roundworm (Caenorhabditis elegans). Also, the major pathways of host defence are covered in light of the response to S. aureus and the similarities and divergences in innate immunity of vertebrates and invertebrates. Consequently, we comparatively consider pathogen recognition receptors, signal transduction pathways (including Toll, Imd and others), and the humoral and cellular antimicrobial effectors. The technically convenient and ethically acceptable invertebrates appear as a valuable first tool to discriminate molecules participating from both sides of the host-S. aureus interaction as well as a high throughput method for antimicrobial screening.     

Invertebrate and fish cytokines

Cytokine-like molecules are well described in invertebrates, although most recent studies have revealed that there is analogy, rather than homology, between invertebrate and vertebrate cytokine-like activities. Cytokines certainly appeared early in the evolution of vertebrates, dating back some 400 millions years. Here, evidence will be reviewed and updated of the presence of these molecules in jawed fish and in particular, in bony fish, which represent the oldest group displaying true functionality of immune system as known in modern vertebrates. Many studies during the last ten years have confirmed the presence of functional homologues of mammalian cytokines in fish. In this review, particular attention will be focussed on IL-1beta, a very ancient defence cytokine recently sequenced in two species, rainbow trout (Oncorhynchus mykiss) and carp (Cyprinus carpio). Original data on the partial peptide sequence of IL-1beta in the mediterranean sea bass Dicentrarchus labrax are also presented.     

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.     

Predator impacts on stream benthic prey

The impact that predators have on benthic, macroinvertebrate prey density in streams is unclear. While some studies show a strong effect of predators on prey density, others show little or no effect. Two factors appear to influence the detection of predator impact on prey density in streams. First, many field studies have small sample sizes and thus might be unable to detect treatment effects. Second, streams contain two broad classes of predators, invertebrates and vertebrates, which might have different impacts on prey density for a variety of reasons, including availability of refuge for prey and prey emigration responses to the two types of predators. In addition, predatory vertebrates have more complex prey communities than predatory invertebrates; this complexity might reduce the impact that predatory vertebrates have on prey because of indirect effects. I conducted a meta-analysis on the results of field studies that manipulate predator density in enclosures to determine (1) if predators have a significant impact on benthic prey density in streams, (2) if the impacts that predatory invertebrates and vertebrates have differ, and (3) if predatory vertebrates have different impacts on predatory prey versus herbivorous prey. The results of the meta-analysis suggest that on average predators have a significant negative effect on prey density, predatory invertebrates have a significantly stronger impact than predatory vertebrates, and predatory vertebrates do not differ in their impact on predatory versus herbivorous invertebrate prey. Three methodological variables (mesh size of enclosures, size of enclosures, and experimental duration) were examined to determine if cross correlations exist that may explain the differences in impact between predatory invertebrates and vertebrates. No correlation exists between mesh size and predator impact. Over all predators, no correlation exists between experimental duration and predator impact; however, within predatory invertebrates a correlation does exist between these variables. Also, a correlation was found between enclosure size and predator impact. This correlation potentially explains the difference in impact between predatory invertebrates and predatory vertebrates. Results of the meta-analysis suggest two important areas for future research: (1) manipulate both types of predators within the same system, and (2) examine their impacts on the same spatial scale.     

Role of gangliosides in the processes of calcium ion transport across the membranes of nerve cells

It has been demonstrated that the content of extracellular Ca in the nervous system is inversely related to the content of gangliosides. The results obtained on invertebrates, lower and higher vertebrates indicate that the highest content of extracellular Ca is typical of the nervous tissue of invertebrates, whereas the lower one--of the nervous tissue of higher vertebrates (mammals). Ganglioside content, on the contrary, is the highest in the brain tissue of the higher vertebrates (mammals and birds), being significantly lower in lower vertebrates; no gangliosides was found at all in the nervous tissue of protostomian invertebrates. The highest ganglioside content in the organism of vertebrates is characteristic to the surface membranes of the nervous cells, especially in the region of synapses. Functional significance of the inverse relationship between the content of extracellular Ca and gangliosides is discussed from the standpoint of one of the authors (R. Veh) who postulated the existence of calcium--ganglioside buffer in the vicinity of the surface of the nervous cells.     

Is vitellogenin an ancestor of apolipoprotein B-100 of human low-density lipoprotein and human lipoprotein lipase?

Vitellogenin, an ancient animal protein, is the major yolk protein of eggs, where it is used as a food source during embryogenesis. Here it is shown that vitellogenins, including those from the invertebrates Caenorhabditis elegans and Drosophila melanogaster, contain domains that are homologous with parts of apolipoprotein B-100 (apoB-100) of human low-density lipoprotein and human lipoprotein lipase. As vitellogenins are likely to have been used by invertebrates during embryogenesis well before the circulation of lipids appeared in vertebrates, it is suggested that copies of a precursor gene, serving a function similar to vitellogenin, were modified to code for part of apoB-100 and lipoprotein lipase in vertebrates. In addition to providing a link between invertebrates and vertebrates for proteins involved in lipid transport, these homologies suggest new functions for vitellogenin other than being a yolk food for the developing embryo.     

Apolipoprotein A-I, an antimicrobial protein in Oncorhynchus mykiss: evaluation of its expression in primary defence barriers and plasma levels in sick and healthy fish

Antimicrobial proteins and peptides play an important role in the primary defence barriers in vertebrates and invertebrates. In a previous study it was shown that high-density lipoprotein (HDL) and its major apolipoproteins, ApoA-I and ApoA-II display antimicrobial activity in the carp (Cyprinus carpio L.). The aim of this study was to evaluate if ApoA-I conserves this defensive function in a salmonid fish like the rainbow trout, in spite of the low level of primary sequence conservation between fish ApoA-I. Here it is shown that trout ApoA-I displays an antimicrobial activity in the micromolar range against Gram positive and Gram negative bacteria, including some fish pathogens. In addition, its expression was also demonstrated by immunohistochemistry and RT-PCR in epidermis, gills and intestinal mucosa, which constitute the main primary defence barriers in fish. Finally, no significant difference in the hepatic expression and plasma levels of this abundant apolipoprotein was found in groups of healthy and diseased fish, in clear contrast with mammals where ApoA-I have been considered a negative acute phase reactant. These findings suggest that ApoA-I could constitute an important innate immunity effector in trout and perhaps other teleost fish.     

Differential expression and costs between maternally and paternally derived immune priming for offspring in an insect

1.?When parasitized, both vertebrates and invertebrates can enhance the immune defence of their offspring, although this transfer of immunity is achieved by different mechanisms. In some insects, immune-challenged males can also initiate trans-generational immune priming (TGIP), but its expressions appear qualitatively different from the one induced by females similarly challenged. 2.?The existence of male TGIP challenges the traditional view of the parental investment theory, which predicts that females should invest more into their progeny than males. However, sexual dimorphism in life-history strategies and the potential costs associated with TGIP may nevertheless lead to dissymmetric investment between males and females into the immune protection of the offspring. 3.?Using the yellow mealworm beetle, Tenebrio molitor, we show that after parental exposure to a bacterial-like infection, maternal and paternal TGIP are associated with the enhancement of different immune effectors and different fitness costs in the offspring. While all the offspring produced by challenged mothers had enhanced immune defence, only those from early reproductive episodes were immune primed by challenged fathers. 4.?Despite the fact that males and females may share a common interest in providing their offspring with an immune protection from the current pathogenic threat, they seem to have evolved different strategies concerning this investment.     

Adrenergic receptor homologies in vertebrate and invertebrate species examined by DNA hybridization

The deduced protein sequences of the mammalian adrenergic receptors (ARs) suggest that these proteins have evolved by several ancient gene duplication events. To investigate in what species these events may have occurred DNA fragments encoding the family of adrenergic receptors from human (beta 1AR and alpha 2AR) and hamster (beta 2AR and alpha 1AR) were used to detect homologous sequences in other vertebrates, invertebrates and unicellular organisms by Southern blot hybridization analysis. Sequences homologous to hamster beta 2AR were detected in lower vertebrates, invertebrates and Dictyostelium, but not in yeast or bacteria. Within vertebrates, sequences strongly homologous to human beta 1AR and human platelet alpha 2AR were confined to the higher vertebrates only. In the invertebrates, only Drosophila contained sequences homologous to hamster alpha 1AR. Our results suggest that non-mammalian species may contain receptors homologous to the mammalian adrenergic receptors and that the sequences homologous to human beta 2AR have been the most strongly conserved.     

Increased tolerance of Litopenaeus vannamei to white spot syndrome virus (WSSV) infection after oral application of the viral envelope protein VP28

It has been generally accepted that invertebrates such as shrimp do not have an adaptive immune response system comparable to that of vertebrates. However, in the last few years, several studies have suggested the existence of such a response in invertebrates. In one of these studies, the shrimp Penaeus monodon showed increased protection against white spot syndrome virus (WSSV) using a recombinant VP28 envelope protein of WSSV. In an effort to further investigate whether this increased protection is limited to P. monodon or can be extended to other penaeid shrimp, experiments were performed using the Pacific white shrimp Litopenaeus vannamei. As found with P. monodon, a significantly lower cumulative mortality for VP28-fed shrimp was found compared to the controls. These experiments demonstrate that there is potential to use oral application of specific proteins to protect the 2 most important cultured shrimp species, P. monodon and L. vannamei, against WSSV. Most likely, this increased protection is based on a shared and, therefore, general defence mechanism present in all shrimp species. This makes the design of intervention strategies against pathogens based on defined proteins a viable option for shrimp culture.     

Organization and function of septate junctions

In most cell types, distinct forms of intercellular junctions have been visualized at the ultrastructural level. Among these, the septate junctions are thought to seal the neighboring cells and thus to function as the paracellular barriers. The most extensively studied form of septate junctions, referred to as the pleated septate junctions, is ultrastructurally distinct with an electron-dense ladder-like arrangement of transverse septa present in invertebrates as well as vertebrates. In invertebrates, such as the fruit fly Drosophila melanogaster, septate junctions are present in all ectodermally derived epithelia, imaginal discs, and the nervous system. In vertebrates, septate junctions are present in the myelinated nerves at the paranodal interface between the myelin loops and the axonal membrane. In this review, we present an evolutionary perspective of septate junctions, especially their initial identification across phyla, and discuss many common features of their morphology, molecular organization, and functional similarities in invertebrates and vertebrates.