Evolution of innate immunity: lessons from mammalian models shaping our current view of insect immunity.

The innate immune system, a cornerstone for organismal resilience against environmental and microbial insults, is highly conserved across the evolutionary spectrum, underpinning its pivotal role in maintaining homeostasis and ensuring survival. This review explores the evolutionary parallels between mammalian and insect innate immune systems, illuminating how investigations into these disparate immune landscapes have been reciprocally enlightening. We further delve into how advancements in mammalian immunology have enriched our understanding of insect immune responses, highlighting the intertwined evolutionary narratives and the shared molecular lexicon of immunity across these organisms. Therefore, this review posits a holistic understanding of innate immune mechanisms, including immunometabolism, autophagy and cell death. The examination of how emerging insights into mammalian and vertebrate immunity inform our understanding of insect immune responses and their implications for vector-borne disease transmission showcases the imperative for a nuanced comprehension of innate immunity's evolutionary tale. This understanding is quintessential for harnessing innate immune mechanisms' potential in devising innovative disease mitigation strategies and promoting organismal health across the animal kingdom.

Unusual and Unexpected Allergic Reactions Can Be Unraveled by Molecular Allergy Diagnostics.

The fifth class of immunoglobulin, immunoglobulin E (IgE) was discovered in 1967 and has had immense importance for the understanding, diagnosis, and treatment of allergic disease. More than 50 years have passed and efforts to characterize, standardize, and refine allergens with the aim to improve clinical diagnosis and allergen-specific immunotherapy are still ongoing. Another important breakthrough was made in 1999 with the introduction of component-resolved diagnostics (CRD), making it possible to quantify IgE antibodies against individual allergen proteins for diagnostic purposes at a molecular level. The progress and developments made in allergy diagnosis often originate from clinical observations and case studies. Observant physicians and health-care personnel have reported their findings in the medical literature, which in turn has inspired researchers to become involved in clinical research. Allergists continuously encounter new allergies and are often asked by their patients how to prevent new reactions. In the current article, we focus on recent clinical observations that can now be explained by CRD. The examples taken concern allergic reactions toward peanuts, tree nuts, lemon kernels, health drinks, meat, insects, dog dander, cannabis, and semen. We now have an improved understanding of why patients may react in a serious or unexpected way, as illustrated by these examples, yet many other clinical observations remain unexplained. The aim of this review is to highlight the importance of clinical observations among allergic patients, focusing on systemic, or unusual and unexpected allergic reactions, where component-testing has further refined the diagnosis of IgE-mediated allergy.

Bronchoalveolar lavage fluid cytokine, cytology and IgE allergen in horses with equine asthma.

The pathophysiology of equine asthma (EA) is still not fully described, but the involvement of an allergic reaction is strongly suspected. This theory has led to the use of allergen-specific immunoglobulin (Ig)E tests to support a diagnosis of asthma. The objective of this descriptive study was to evaluate the correlation between four subgroups of EA (mastocytic mild equine asthma [MEA], neutrophilic MEA, mixed MEA, and severe equine asthma [SEA]), allergen specific IgE (measured in both serum and BALF) and mRNA expression of selected genes in bronchoalveolar lavage fluid (BALF). Serum and BALF were collected from 64 horses with a history of lower airway problems with or without poor performance. Differential cell counts from BALF were used to assign horses to one of four groups (mastocytic MEA; neutrophilic MEA, mixed MEA, and SEA). The expression of messenger RNA (mRNA) coding for IL4, IL5, IL8, IL10, TGFB, TNFA, toll-like receptor (TLR)4, IL1RA, IL1B, matrix metalloproteinase 8 (MMP8), TLR9, chemokine ligand 5 (CCL5) and cluster of differentiation (CD)14 in BALF were measured using reverse transcriptase (RT) quantitative PCR (qPCR). Allergen-specific IgE was measured in serum and BALF using an allergen-specific IgE ELISA test with the screening panel: house mites, storage mites, mould and pollen. As expected, the BALF neutrophil differential count correlated with mRNA expression of MMP-8 (r = 0.611, p < 0.001), TLR-4 (r = 0.540, p < 0.001), IL-1RA (r = 0.490, p < 0.001), IL-1ß (r = 0.463, p < 0.001) and IL-8 (r = 0.302, p = 0.015). Cytokine expression of IL-1ß (p = 0.014), MMP8 (p = 0.028) and IL-1RA (p = 0.037) was significantly higher in the SEA group compared to the MEA subgroups. The BALF mast cell count was correlated with allergen-specific IgE for insects (r = 0.370, p = 0.002) and pollen (r = 0.313, p = 0.011). Eosinophils in BALF were correlated with BALF mRNA expression of IL-4 (r = 0.340, p = 0.006) together with a significant correlation between BALF eosinophils and allergen-specific IgE for mites (r = 0.930, p < 0.001) and pollen in BALF (r = 0.837, p < 0.001). No correlation was found between allergen-specific IgE in serum and BALF for any of the allergen in the screening panel. Based on these results from allergen-specific IgE in horses with EA is not found in systemic circulation, and only the mastocytic and mixed subgroups of horses with EA had allergen-specific IgE in BALF. Further studies are needed to clarify the relationships identified here.

A theoretical exploration of dietary collective medication in social insects.

Animals often alter their food choices following a pathogen infection in order to increase immune function and combat the infection. Whether social animals that collect food for their brood or nestmates adjust their nutrient intake to the infection states of their social partners is virtually unexplored. Here we develop an individual-based model of nutritional geometry to examine the impact of collective nutrient balancing on pathogen spread in a social insect colony. The model simulates a hypothetical social insect colony infected by a horizontally transmitted parasite. Simulation experiments suggest that collective nutrition, by which foragers adjust their nutrient intake to simultaneously address their own nutritional needs as well as those of their infected nestmates, is an efficient social immunity mechanism to limit contamination when immune responses are short. Impaired foraging in infected workers can favour colony resilience when pathogen transmission rate is low (by reducing contacts with the few infected foragers) or trigger colony collapse when transmission rate is fast (by depleting the entire pool of foragers). Our theoretical examination of dietary collective medication in social insects suggests a new possible mechanism by which colonies can defend themselves against pathogens and provides a conceptual framework for experimental investigations of the nutritional immunology of social animals.

Aeroallergens, atopy and allergic rhinitis in the Middle East.

The literature on the nature and prevalence of indoor and/or outdoor aeroallergens, atopy and symptoms of rhinitis and asthma in the Middle East region (defined here as Bahrain, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Kingdom of Saudi Arabia - KSA, Syria, United Arab Emirates and Yemen) was reviewed. Although documentation was poor in all countries other than Iran and the KSA, a wide range of "global" and "local" aeroallergens (grass, weed and tree pollens, fungal spores, insect allergens, dander, and house dust mites) has been observed across the region. The prevalence of current self-reported or parent-reported symptoms of rhinitis ranged from 9% to 38%. Researchers have suggested that the high atopy rates and self-reported rhinitis rates are associated with an on-going shift towards a "western" lifestyle.

Transcriptomic immune response of the cotton stainer Dysdercus fasciatus to experimental elimination of vitamin-supplementing intestinal symbionts.

The acquisition and vertical transmission of bacterial symbionts plays an important role in insect evolution and ecology. However, the molecular mechanisms underlying the stable maintenance and control of mutualistic bacteria remain poorly understood. The cotton stainer Dysdercus fasciatus harbours the actinobacterial symbionts Coriobacterium glomerans and Gordonibacter sp. in its midgut. The symbionts supplement limiting B vitamins and thereby significantly contribute to the host's fitness. In this study, we experimentally disrupted the symbionts' vertical transmission route and performed comparative transcriptomic analyses of genes expressed in the gut of aposymbiotic (symbiont-free) and control individuals to study the host immune response in presence and absence of the mutualists. Annotation of assembled cDNA reads identified a considerable number of genes involved in the innate immune system, including different protein isoforms of several immune effector proteins (specifically i-type lysozyme, defensin, hemiptericin, and pyrrhocoricin), suggesting the possibility for a highly differentiated response towards the complex resident microbial community. Gene expression analyses revealed a constitutive expression of transcripts involved in signal transduction of the main insect immune pathways, but differential expression of certain antimicrobial peptide genes. Specifically, qPCRs confirmed the significant down-regulation of c-type lysozyme and up-regulation of hemiptericin in aposymbiotic individuals. The high expression of c-type lysozyme in symbiont-containing bugs may serve to lyse symbiont cells and thereby harvest B-vitamins that are necessary for subsistence on the deficient diet of Malvales seeds. Our findings suggest a sophisticated host response to perturbation of the symbiotic gut microbiota, indicating that the innate immune system not only plays an important role in combating pathogens, but also serves as a communication interface between host and symbionts.

Assessment of serum levels of allergen-specific immunoglobulin E in different seasons and breeds in healthy horses.

The present study was designed to asses specific IgE towards environment allergens in 42 healthy horses. Determination of this immunoglobulin in serum serve as diagnostic tools in allergic diseases to improve efficacy of the treatment and proper allergen selection to specific immunotherapy. Serum levels of allergen specific IgE were measured with equine monoclonal antibody, using 15 individual and 5 mix allergens in North European Panel. The study revealed season dependent increased levels of allergen specific IgE in normal horses. It is noteworthy that healthy horses show high percentage of positive reactions, most commonly towards to domestic mites D. farinae (80%), D. pteronyssinus (35.71%) and storage mites T. putrenscentiae (42.86%), Acarus siro (40.48%). These allergens play an important role in equine, canine and feline atopic dermatitis. We also demonstrated high IgE levels in the group of horse specific insect allergens. Tabanus sp. (35.71%), Culicoides sp. (28.57%) and Simulium sp. (26.19%) were the most frequent insect positive reaction allergens. No positive reactions in all groups of allergens were found in winter season, low and merely detectable levels of antibodies have been found relating to D. farianae and T. putrescentiae allergen. We observed elevated mould-IgE levels in horses that live in stables, while outdoor living horses showed very low levels. Amongst all positive reactions we observed only weak and moderate reactions but no strong positive reactions were found. No significant differences were observed between three breeds of horses with the exception of moulds and D. pteronyssinus allergens.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

Standardization of allergen extracts.

Allergens are molecules with the capacity to elicit IgE responses in humans. When stimulated with allergens, most allergic patients respond with production of IgE specific for several proteins/allergens in the source material. The standardization of allergen extracts is essential in order to control variability and to achieve consistency and reproducibility in a clinical setting. Because the IgE binding capacity of an allergen extract is related to the content of one or a few major allergens, it is important that the standardization procedure ensures consistency, not only in the overall IgE binding potency, but also in the content and ratio of individual major allergens. Owing to the complexity of allergen extracts, a key element in standardization of allergen extracts is the use of standards. This chapter describes the principles for standardization of allergen extracts to be used by research laboratories. Other chapters in this volume describe methods in detail.

Comparative psychoneuroimmunology: evidence from the insects.

Interactions between immune systems, nervous systems, and behavior are well established in vertebrates. A comparative examination of these interactions in other animals will help us understand their evolution and present adaptive functions. Insects show immune-behavioral interactions similar to those seen in vertebrates, suggesting that many of them may have a highly conserved function. Activation of an immune response in insects results in illness-induced anorexia, behavioral fever, changes in reproductive behavior, and decreased learning ability in a broad range of species. Flight-or-fight behaviors result in a decline in disease resistance. In insects, illness-induced anorexia may enhance immunity. Stress-induced immunosuppression is probably due to physiological conflicts between the immune response and those of other physiological processes. Because insects occupy a wide range of ecological niches, they will be useful in examining how some immune-behavioral interactions are sculpted by an animal's behavioral ecology.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects.

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported primarily in the Journal in 2005. Although studies documented deficiencies in community management of anaphylaxis, guidelines and National Institutes of Health summary reports provide direction toward improved research and education. At least 9% of young children "outgrow" a tree nut allergy. Advances in food allergy diagnosis include reports of probability of reactions to peanut at various peanut-specific IgE concentrations and skin test response size and the utility of evaluating IgE binding to specific epitopes. Future food allergy treatments might include selection of "less allergenic" fruit cultivars, genetic silencing of major allergens, and treatment of allergic patients with Chinese herbal remedies. Osteopontin might be a useful biomarker for success of venom immunotherapy. Progress in our understanding of the immunology of atopic dermatitis and autoimmune urticaria has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.

[Regional features of sensitization of children to some noninfectious allergens]. / Regional'nye osobennosti sensibilizatsii organizma detei k nekotorym heinfektsionnym allergenam.

The results of epidemiological investigations within the frames of the ISAAC program are presented. Out of 2,870 children, 172 children (6.0%) with sensitization to some noninfectious (insect, pollen, medicinal) allergens were detected. The number of allergic children was found to be 10.4 +/- 1.8 to 28.2 +/- 3.0 per 1000 of urban child population. Specific features of the sensitization of urban children to regional insect, pollen and medicinal allergens were established. The clinical course of allergic diseases in children was characterized by polymorphism and a great variety of clinical symptoms with frequent lesions of the gastrointestinal tract and functional disturbances of the central nervous system, which adversely affected the school studies of children and the quality of their life. In the development of allergy in children such factors of risk as hereditary predisposition to allergy, allergic diathesis, focal infections and artificial feeding during the first year of life were also of great importance.

Recombinant allergens for skin testing.

Skin testing is a basic diagnostic procedure widely used to explore immediate-type reactions to allergen preparations in vivo. Despite their reliability, if standardized extracts are used, skin tests suffer from limited reproducibility due to difficulties in preparing consistently standardized extracts from natural raw material. Starting from allergen-encoding cDNAs, large amounts of highly pure allergens with a high batch-to-batch consistency satisfying the quality requirements of medicinal products manufactured by recombinant DNA technology can be produced. These reagents are expected to be qualitatively superior to the commercially available allergen preparations used for the in vitro and in vivo diagnosis of allergic conditions. In this article the current literature available on skin testing with such recombinant allergens (rAllergens) is reviewed and critically analyzed. To date many different rAllergens of various pollens, moulds, mites, bee venom, latex and celery have been used in skin testing in more than 1,600 allergic and control individuals. Skin prick tests as well as intradermal skin tests with rAllergens prove to be highly specific and safe. The diagnostic sensitivity of single rAllergens is generally lower than those obtained with allergen extracts, but can be considerably increased by using rAllergen panels covering the most important allergenic structures present in a given complex allergenic extract. Moreover, quantitative skin testing with single rAllergens allows interesting insights into correlations between the in vivo and in vitro sensitization to a given allergen. In conclusion, skin testing with rAllergens offers a highly specific and safe additional diagnostic tool to elucidate patient- and disease-specific sensitization patterns which will be needed for the development of patient-tailored immunotherapeutic treatments.

[Allergens]. / Les allergenes.

The clinical signs linked with immediate hypersensitivity, correspond with an abnormal reactivity of the immune system, which appears following contact with external substances, the allergens. Over the last few years there has been considerable progress in research on these substances in the domain of structural characterisation, biochemistry and immunological properties. Besides the definition of the word allergen linked to its immunological characteristics, our usual language maintains a certain ambiguity in its use which may characterise different states, including successive steps of the manufacture of an allergen extract. In effect the word allergen may designate the agent that is responsible for the allergic disease, for example cat, but also the raw material used for the manufacture of the corresponding extract, whether it be hair or squames; it may also apply to the final allergenic extract, the extract of cat hair or squames, as well as a precise molecule such as the major allergen of cat Fel d1 in the same example. After having reviewed several definitions as well as the nomenclature we will study the general characteristics of pneumoallergens and trophallergens, those of recombinant allergens, then the parameters of manufacture of allergen extracts.

[Allergens causing respiratory allergy: the aeroallergens]. / Allergènes responsables d'allergie respiratoire: les pneumallergènes.

Aeroallergens play a major role in the pathogenesis of allergic diseases, particularly asthma and rhinitis. Indoor allergens, including house dust mites, domestic pets, cockroaches, and molds are of particular importance. Pollens are also recognized as a major source of allergens. The role of these different allergens varies with environment conditions, such as climatic factors, and degree of exposure. Knowledge about allergens has progressed, especially with recent molecular biology studies. Structure and function have been identified. These studies have provided explanations about the relationship between allergic sensitization, allergen exposure, and disease activity, about clinical observations such as allergic cross reactions, and improvement in the production of allergenic extracts (necessary to diagnosis and immunotherapy). Environmental control measures are of particular importance in the prevention and management of allergic diseases.

Inhalant allergens: as a cause of respiratory allergy in east Mediterranean area, Turkey.

Inhalant allergens were identified by analyzing the positive skin tests of 614 respiratory allergic patients. The important indoor allergens causing skin test positivity were house dust, Dermatophogoides pteronyssinus, cockroach, mosquito and Dermatophogoides farinea. Johnson grass, cultivated wheat, rye, orchard, and cultivated corn were among important grass pollens. Animal allergens like cow hair, cat and dog dander, bird and chicken feathers and horse hair caused skin test positivity in our allergic patients. Weeds and garden plants were also among important inhalant allergens in this region. Common cocklebur, narcissus, rose, mugworth, and daisy caused skin test positivity in decreasing frequencies. Carob, willow, poplar, olive and cypress pollens were among important inhalant allergens causing skin test positivity that may be important cause of respiratory allergy in this region.

Aeroallergens in dairy barns near Cooperstown, New York and Rochester, Minnesota.

We sampled atmospheric barn air using a volumetric air sampler in ten barns near Cooperstown, NY and six barns near Rochester, MN, and, with radioimmunoassays, measured allergens of Aspergillus fumigatus, Thermoactinomyces vulgaris, Micropolyspori faeni, short ragweed, rye grass group I pollen, Alternaria (Alt-1), Dermatophagoides sp. Lepidoglyphus destructor, common insect allergen, mouse urine, rat urine, and cattle epithelium. The most abundant allergen present was A. fumigatus followed by L. destructor. This study provides initial data on barn aerobiology and demonstrates for the first time the abundance of L. destructor allergens in North American dairy barns. More comprehensive study of barns, poultry houses, confinement houses for swine, and other agricultural environments from various geographic locations is needed to define the allergen levels to which millions of farm workers are exposed each day. While most of the allergens were expected, the presence of airborne allergens reactive with antisera to Dermatophagoides suggests indirectly that substantial amounts of pyroglyphid mites are present in some barns.