Invertebrate and vertebrate neuroimmune and autoimmunoregulatory commonalties involving opioid peptides

1. Evidence for bidirectional interrelationships between the nervous system and immune systems of vertebrates and invertebrates involving opioid peptides is briefly discussed. 2. The involvement of opioid peptides in autoimmunoregulatory communication also is discussed. 3. The presence of mammalian interleukin-like (1 & 6) and tumor necrosis factor-like molecules in invertebrates is reviewed as well as an apparent cascading system for these signal molecules. 4. The significance of ACTH and MSH in cellular immunosuppression and autoimmunoregulation is discussed in the context of a potential role in schistosomiasis and human immunodeficiency virus actions. 5. The review concludes with the hypothesis that the mammalian immune system has its origin in the invertebrate immune/defense system given the many similarities noted in the review based on new knowledge about the more "primitive" system.     

Comparing the invasibility of experimental "reefs" with field observations of natural reefs and artificial structures

Natural systems are increasingly being modified by the addition of artificial habitats which may facilitate invasion. Where invaders are able to disperse from artificial habitats, their impact may spread to surrounding natural communities and therefore it is important to investigate potential factors that reduce or enhance invasibility. We surveyed the distribution of non-indigenous and native invertebrates and algae between artificial habitats and natural reefs in a marine subtidal system. We also deployed sandstone plates as experimental 'reefs' and manipulated the orientation, starting assemblage and degree of shading. Invertebrates (non-indigenous and native) appeared to be responding to similar environmental factors (e.g. orientation) and occupied most space on artificial structures and to a lesser extent reef walls. Non-indigenous invertebrates are less successful than native invertebrates on horizontal reefs despite functional similarities. Manipulative experiments revealed that even when non-indigenous invertebrates invade vertical "reefs", they are unlikely to gain a foothold and never exceed covers of native invertebrates (regardless of space availability). Community ecology suggests that invertebrates will dominate reef walls and algae horizontal reefs due to functional differences, however our surveys revealed that native algae dominate both vertical and horizontal reefs in shallow estuarine systems. Few non-indigenous algae were sampled in the study, however where invasive algal species are present in a system, they may present a threat to reef communities. Our findings suggest that non-indigenous species are less successful at occupying space on reef compared to artificial structures, and manipulations of biotic and abiotic conditions (primarily orientation and to a lesser extent biotic resistance) on experimental "reefs" explained a large portion of this variation, however they could not fully explain the magnitude of differences.     

Multiple Effects of Introduced Mammalian Herbivores in a Temperate Forest

Introduced mammalian herbivores can significantly affect ecosystems. Here, I review evidence on effects of introduced mammalian herbivores in the temperate forest of the southern Andes. Available data suggest that introduced herbivores decrease the abundance of seedlings and saplings of dominant tree species in some forest types, which could impair forest regeneration. They also affect understory species composition. The mechanisms of the effects of introduced herbivores are complex, and include direct effects of browsing or trampling and more complex interactions such as indirect effects through other species. Some native mammalian and avian predators may benefit from increased food availability resulting from high densities of some introduced mammalian herbivores. In turn, enhanced populations of predators may have resulted in increased predation on native prey. Competition for resources and disease transmission have also been proposed as possible negative effects of introduced herbivores on native herbivores, but little evidence supports this claim. Little is known about effects on invertebrates.     

Cell Cultures from Marine Invertebrates: New Insights for Capturing Endless Stemness

Despite several decades of extensive research efforts, there is yet no single permanent cell line available from marine invertebrates as these cells stop dividing in vitro within 24–72 h after their isolation, starting cellular quiescence. This ubiquitous quiescent state should be modified in a way that at least some of the quiescent cells will become pluripotent, so they will have the ability to divide and become immortal. Following the above need, this essay introduces the rationale that the discipline of marine invertebrates’ cell culture should gain from applying of two research routes, relevant to mammalian systems but less explored in the marine arena. The first is the use of adult stem cells (ASC) from marine organisms. Many marine invertebrate taxa maintain large pools of ASC in adulthood. Ample evidence attests that these cells from sponges, cnidarians, flatworms, crustaceans, mollusks, echinoderms, and ascidians play important roles in maintenance, regeneration, and asexual cloning, actively proliferating in vivo, resembling the vertebrates’ cancer stem cells features. The second route is to target resting somatic cell constituents, manipulating them in the same way as has recently been performed on mammalian induced pluripotent stem (iPS) cells. While “iPS cells” are the outcome of an experimental manipulation, ASC are natural and rather frequent in a number of marine invertebrates. Above two cell categories reveal that there are more than a few types of seeds (cells) waiting to be sowed in the right soil (in vitro environmental conditions) for acquiring stemness and immortality. This rationale carries the potential to revolutionize the discipline of marine invertebrate cell cultures. When cultured “correctly,” ASC and “iPS cells” from marine invertebrates may stay in their primitive stage and proliferate without differentiating into cells lineages, harnessing the stem cell’s inherent abilities of self-replication versus differentiated progenies, toward the development of immortal cell lines.     

Effect of low doses of ionizing radiation on cells cultured from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus

Explant cultures from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus, were exposed to low doses of (60)Co gamma radiation. Cells growing from the explants were examined 7 days after irradiation using light and transmission electron microscopy and were also tested for their ability to produce signals indicative of a bystander effect. The exposed cultures displayed pronounced damage and were orders of magnitude more sensitive than the data in the literature would suggest for arthropod cells. The cultures were also more sensitive than mammalian cells that were exposed to similar doses. Cellular abnormalities included damage to cytoplasmic organelles, particularly the cytoskeleton. Abnormal mitochondria were also prominent. At low doses (0.5 Gy), nuclear damage was not apparent in the cultures, but there was evidence of a dose-dependent increase in apoptosis. The irradiated cultures released a factor into the medium that was capable of inducing apoptosis and cell death in unirradiated fish and human cells. This bystander effect was of a similar magnitude to that reported for mammalian cell systems. It is suggested that these crustaceans may be highly sensitive to radiation, unlike terrestrial arthropods and certain other invertebrates, which are generally considered to be radioresistant.     

Trained immunity: a memory for innate host defense

Immune responses in vertebrates are classically divided into innate and adaptive, with only the latter being able to build up immunological memory. However, although lacking adaptive immune responses, plants and invertebrates are protected against reinfection with pathogens, and invertebrates even display transplant rejection. In mammals, past "forgotten" studies demonstrate cross-protection between infections independently of T and B cells, and more recently memory properties for NK cells and macrophages, prototypical cells of innate immunity, have been described. We now posit that mammalian innate immunity also exhibits an immunological memory of past insults, for which we propose the term "trained immunity." Understanding trained immunity will revolutionize our view of host defense and immunological memory, and could lead to defining a new class of vaccines and immunotherapies.     

The phylogenetic odyssey of the erythrocyte. II. The early or invertebrate prototypes

Freely existing hemoglobin-bearing cells suspended in a plasmic milieu (erythrocytes) are found in a relatively small number of taxanomically scattered invertebrates. These species include some annelids, echiurids, molluscs, phoronids, nemerteans and echinoderms, e.g. Pista pacifica, Urechis caupo, Noetia ponderosa, Phoronis australis, Lineus fuscoviridis and Cucumaria miniata respectively. The typical invertebrate erythrocyte (hemocyte, coelomocyte) can be described as permanently nucleated, considerably larger than the human red cell, oval or circular in configuration and spherical, biconvex or flattened in profile. The marginal band of the erythrocyte, a bundle of subplasmalemmal microtubules that circumscribes the periphery of the cell and lies in the plane parallel to its flat surface makes its first appearance in certain invertebrates. This structure in association with the cell surface-associated cytoskeleton is responsible for the flattened elliptical shape seen in some invertebrate erythrocytes and endows them with flexibility and resilience to mechanical forces. This in an evolutionarily persistent characteristic that is retained throughout the submammalian vertebrates. The erythrocytes of invertebrates are more morphologically and functionally diversified than the mammalian model. In addition to respiratory activities (oxygen storage and transport) they can sometimes function as vendors of nutrients and participate in other less obvious processes. These cells therefore frequently not only retain organelles that are usually discarded by vertebrate erythrocytes (ribosomes, golgi apparatus, etc.) but may also depending upon the species, manifest in their cytoplasm organelles and inclusions that are not a normal component of developing or mature submammalian vertebrate and mammalian erythroid cells. Examples of the latter are pigment granules, lipid droplets, extensive glycogen stores and prominent Prussian blue positive inclusions. Erythrocytes in the invertebrates, though presenting certain cytologic and functional features in common, are a heterogenous collection of cells, each tailored for a specific species or group of organisms.     

d-Amino acids in brain neurotransmission and synaptic plasticity

Far from our initial view of d-amino acids as being limited to invertebrates, they are now considered active molecules at synapses of mammalian central and peripheral nervous systems, capable of modulating synaptic communication within neuronal networks. In particular, experimental data accumulated in the last few decades show that through the regulation of glutamatergic neurotransmission, d-serine influences the functional plasticity of cerebral circuitry throughout life. In addition, the modulation of NMDA-R-dependent signalling by d-aspartate has been demonstrated by pharmacological studies and after the targeted deletion of the d-aspartate-degrading enzyme. Considering the major contribution of the glutamatergic system to a wide range of neurological disorders such as schizophrenia, Alzheimer’s disease and amyotrophic lateral sclerosis, an improved understanding of the mechanisms of d-amino-acid-dependent neuromodulation will certainly offer new insights for the development of relevant strategies to treat these neurological diseases.     

Comparative immunologic models can enhance analyses of environmental immunotoxicity

To treat immune systems and how environments affect them is a unique challenge especially when the environment is considered in its broadest perspective: internal and external. Internal focuses on relationships between immune, nervous and endocrine systems (neuroendocrine) and how they interact to maintain homeostasis. External considers physical and chemical influences that act to change the internal. Using animal models is based upon phylogeny which focuses on invertebrates, fish, amphibians, and reptiles, including mammalian results and relationships to humans. Emphasizing primitive animals is due to a growing interest in using them as models, sentinels, surrogates—predictors of what may happen when the environment is disturbed. They are inexpensive, socially acceptable, and since they live in diverse habitats under natural conditions, what may happen to them may be more applicable to humans than to laboratory reared models (sometimes inbred) whose controlled habitats may not be considered as natural. Humans do not live in controlled laboratories but like numerous animals, we do live in various climates, under different conditions of light, temperature, crowding, seasons and in different habitats that determine the quality of life including the susceptibility to disease. The immune system is affected by these influences, and it in turn is responsible for the body's surveillance against these threats.     

Regulatory peptides in parasitic platyhelminths

Regulatory peptides are short chains of amino acids that regulate cell-to-cell interactions in widely divergent animal groups. Evidence is accumulating to suggest that they mediate many aspects of physiology and behaviour, serving as neurotransmitters, neuromodulators and hormones. While most data in this field derive from studies on the mammalian nervous and endocrine systems, the last decade has witnessed an upsurge of interest in invertebrate peptide biology, not least because it is likely that many regulatory peptides originated in the nervous system of invertebrates. Platyhelminths, like other invertebrate groups investigated, contain numerous neuropeptides, and here David Halton and colleagues review the evidence that these putative signalling agents serve key roles in parasite motility, reproduction and morphogenesis. The physicochemical differences between host and parasite peptides raise the possibility that selective disruption of peptidergic control systems in parasites could be an exploitable target in future chemotherapeutic strategies.     

Direct consumptive interactions between mammalian herbivores and plant-dwelling invertebrates: prevalence,significance, and prospectus

Mammalian herbivores induce changes in the chemical composition, phenology, distribution, and abundance of the plants they feed on. Consequently, invertebrate herbivores (predominantly insects) that depend on those plants, and the predators and parasitoids that are associated with them, may be affected. This plant-mediated indirect interaction between mammals and invertebrates has been extensively studied, but mammalian herbivores may also directly affect plant-dwelling invertebrates (PDI) by incidentally ingesting them while feeding. The ubiquity and small size of PDI render them highly susceptible to incidental ingestion, but as common as this interaction may intuitively seem, very little is known about its prevalence and ecological consequences. Nevertheless, cases of incidental ingestion of PDI and associated adaptations for avoiding it that have been sporadically documented in several invertebrate groups and life stages allow us to carefully extrapolate and conclude that it should be common in nature. Incidental ingestion may, therefore, bear significant consequences for PDI, but it may also affect the mammalian herbivores and the shared plants. Future research on incidental ingestion of PDI would have to overcome several technical difficulties to gain better insight into this understudied ecological interaction.     

Insect galectins: roles in immunity and development

As evidenced by the reviews in this special issue of Glycoconjugate Journal, much research is focused on determining functions for mammalian galectins. However, the identification of precise functions for mammalian galectins may be complicated by redundancy in tissue expression and in target cell recognition of the many mammalian galectins. Therefore, lower organisms may be useful in deciphering precise functions for galectins. Unfortunately, some genetically manipulable model systems such as Caenorhabditis elegans may have more galectins than mammals. Recently, galectins were identified in two well-studied insect systems, Drosophila melanogaster and Anopheles gambiae. In addition to the powerful genetic manipulation available in these insect models, there is a sophisticated understanding of many biological processes in these organisms that can be directly compared and applied to mammalian systems. Understanding the roles of galectins in insects may provide insight into precise functions of galectins in mammals.     

Two different evolutionary origins of stem cell systems and their molecular basis

We propose two major evolutionary origins of stem cell systems in the animal kingdom. Adult pluripotent stem cell systems are found in many invertebrates and probably evolved as components of asexual reproduction. Lineage-specific stem cell systems probably evolved later and include neural and hematopoietic stem cell types. We propose that these two types of stem cell systems evolved independently. The vasa-like genes regulate reproductive stem cells, but not lineage-specific stem cells, which may be regulated by gcm genes. Here, we review the evidence for the molecular basis for the evolutionary origin of these two different stem cell systems.     

A novel role for an insect apolipoprotein (apolipophorin III) in beta-1,3-glucan pattern recognition and cellular encapsulation reactions

Lipoproteins and molecules for pattern recognition are centrally important in the innate immune response of both vertebrates and invertebrates. Mammalian apolipoproteins such as apolipoprotein E (apoE) are involved in LPS detoxification, phagocytosis, and possibly pattern recognition. The multifunctional insect protein, apolipophorin III (apoLp-III), is homologous to apoE. In this study we describe novel roles for apoLp-III in pattern recognition and multicellular encapsulation reactions in the innate immune response, which may be of direct relevance to mammalian systems. It is known that apoLp-III stimulates antimicrobial peptide production in insect blood, enhances phagocytosis by insect blood cells (hemocytes), and binds and detoxifies LPS and lipoteichoic acid. In the present study we show that apoLp-III from the greater wax moth, Galleria mellonella, also binds to fungal conidia and beta-1,3-glucan and therefore may act as a pattern recognition molecule for multiple microbial and parasitic invaders. This protein also stimulates increases in cellular encapsulation of nonself particles by the blood cells and exerts shorter term, time-dependent, modulatory effects on cell attachment and spreading. All these responses are dose dependent, occur within physiological levels, and, with the notable exception of beta-glucan binding, are only observed with the lipid-associated form of apoLp-III. Preliminary studies also established a beneficial role for apoLp-III in the in vivo response to an entomopathogenic fungus. These data suggest a wide range of immune functions for a multiple specificity pattern recognition molecule and may provide a useful model for identifying further potential roles for homologous proteins in mammalian immunology, particularly in terms of fungal infections, pneumoconiosis, and granulomatous reactions.     

In the laboratory and during free-flight: old honey bees reveal learning and extinction deficits that mirror mammalian functional decline

Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction). Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models.     

Allorecognition and chimerism in an invertebrate model organism

The presence of highly specific histocompatibility reactions in colonial marine invertebrates that lack adaptive immune systems (such as the sponges, cnidarians, bryozoans and ascidians) provides a unique opportunity to investigate the evolutionary roots of allorecognition and to explore whether homologous innate recognition systems exist in vertebrates. Conspecific interactions among adult animals in these groups are regulated by highly specific allorecognition systems that restrict somatic fusion to self or close kin. In Hydractinia (Cnidaria:Hydrozoa), fusion/rejection responses are controlled by two linked genetic loci. Alleles at each locus are co-dominantly inherited. Colonies fuse if they share at least one haplotype, reject if they share no haplotypes, and display transitory fusion if they share only one allele in a haplotype—a pattern that echoes natural killer cell responses in mice and humans. Allorecognition in Hydractinia and other marine invertebrates serves as a safeguard against stem cell or germline parasitism thus, limiting chimerism to closely related individuals. These animals fail to become tolerant even if exposed during early development to cells from a histoincompatible individual. Detailed analysis of the structure and function of molecules responsible for allorecognition in basal marine invertebrates could provide clues to the innate mechanisms by which higher animals respond to organ and cell allografts, including embryonic tissues.Key words: allorecognition, chimerism, invertebrate, innate immune system     

Can color vision variation explain sex differences in invertebrate foraging by capuchin monkeys?

Invertebrates are the main source of protein for many small-to-medium sized monkeys. Prey vary in size, mobility, degree of protective covering, and use of the forest, I.e. Canopy height, and whether they are exposed or embed themselves in substrates. Sex-differentiation in foraging patterns is well documented for some monkey species and recent studies find that color vision phenotype can also affect invertebrate foraging. Since vision phenotype is polymorphic and sex-linked in most New World monkeys - males have dichromatic vision and females have either dichromatic or trichromatic vision - this raises the possibility that sex differences are linked to visual ecology. We tested predicted sex differences for invertebrate foraging in white-faced capuchins Cebus capucinus and conducted 12 months of study on four free-ranging groups between January 2007 and September 2008. We found both sex and color vision effects. Sex: Males spent more time foraging for invertebrates on the ground. Females spent more time consuming embedded, colonial invertebrates, ate relatively more "soft" sedentary invertebrates, and devoted more of their activity budget to invertebrate foraging. Color Vision: Dichromatic monkeys had a higher capture efficiency of ex posed invertebrates and spent less time visually foraging. Trichromats ate relatively more "hard" sedentary invertebrates. We con clude that some variation in invertebrate foraging reflects differences between the sexes that may be due to disparities in size, strength, reproductive demands or niche preferences. However, other intraspecific variation in invertebrate foraging that might be mistakenly attributed to sex differences actually reflects differences in color vision.     

Spatiotemporal variation of Diptera changes how we evaluate High Nature Value (HNV) wet grasslands

Proposed strategies to protect biodiversity within agricultural systems are often based on botanical criteria with plant species richness generally considered the prime indicator of conservation potential. While wet grasslands dominated by rushes (Juncus spp.) are commonly considered to be of lesser ecological value than those which are more botanically diverse (e.g. Carex dominated wet grasslands), their value for invertebrates such as Diptera has not yet been fully explored. Data from two Diptera families (Sciomyzidae and Syrphidae) were examined at spatial, temporal and spatiotemporal scales to determine the contribution of two different (Juncus and Carex dominated) wet grassland habitats towards the maintenance of Diptera diversity. The two habitats were significantly different in terms of community structure for both families and temporal variation was a significant component of dipteran diversity. Spatiotemporal analysis showed that species turnover between habitats at different times made the most significant contribution to overall Diptera diversity. Temporal variation of both families suggests that the relative importance of each habitat type to overall diversity fluctuates depending on sampling period, with both habitats supporting diversity at different times. Our results indicate that lowland wet grasslands characterised by Juncus cover need to be recognised as ecologically important for the maintenance of dipteran diversity. We discuss the possible implications for the diversity of Diptera in wet grasslands if these commonly perceived marginal areas (both agriculturally and ecologically) are ignored in conservation strategies. The necessity of recognising spatiotemporal variation when evaluating habitats using invertebrates as indicators is also discussed.     

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.