Human Allergy Research Articles

Characterization of Potential Pathogenic Cladosporium Exposure Risks from Heating, Ventilation and Air Conditioning (HVAC) in Two Cities, China

Cladosporium is widespread in Heating, Ventilation and Air Conditioning (HVAC). Some species in which are responsible for the majority of fungal infections or allergy in humans. To assess the exposure risks of Cladosporium in HVAC to human health, the colony distribution, population constituent and pathogenic species identification of Cladosporium were investigated in current study. We selected two cities, Beijing and Nanjing, representing the North and South of China respectively, for the study. Three kinds of public places including hospitals, hotels and super markets were selected and 108 air samples from 18 sampling sites were collected from air supply outlets of HVAC in summer, 2012. The collecting plates were incubated at 28°C for 2-3 weeks. Purified fungal colonies were identified at the genus and species level based on morphological and DNA sequences. Internal transcribed spacer ITS1 and ITS2 region, partial gene sequences of the translation elongation facter1-α gene (EF-1α) and the actin gene (ACT) were used for phylogenetic analysis. Among all genera detected, Cladosporium was identified to have the widest prevalence (92.3%) from HVAC, which was detected from 100 of 108 air samples. 9 species of Cladosporium were identified viz. C. breviramosum, C. cladoporioides, C. cucumerinum, C. gossypiicola, C. macrocarpum, C. perangustum, C. sp., C. sphaerospermum and C. tenuissimum. Among of them, C. cladosporioides had the highest concentration and frequency, considered as predominant species in HVAC. There were three species, C. cladoporioides, C. sphaerospermum and C. macrocarpum, distributed as opportunistic pathogen to human reported before. The total frequency of the three species was 76.29% of this genus. What’s more, C. cladoporioides and C. sphaerospermum were detected in both cities with relatively high concentration and frequency. The frequency and prevalence rate in the South were higher than those in the North, suggesting that HVAC in the South was more susceptable to Cladosporium contamination.

Method for collecting mouse milk without exogenous oxytocin stimulation.

It has been reported that breast-feeding more than 6 months strongly decreases the risk of allergy, diabetes, obesity, and hypertension in humans. In order to understand the mechanisms responsible for this benefit, it is important to evaluate precisely the composition of maternal milk, especially in response to environmental cues. Mouse models offer a unique opportunity to study the impact of maternal milk composition on the development and health of offspring. Oxytocin injection of the dam is usually used to stimulate milk ejection; however, exogenous oxytocin might have deleterious effects under some experimental conditions by modifying milk content as well as the physiology and behavior of the dam. Taking advantage of the natural stimulation of the mammary gland that occurs after the reunion of a dam that has been separated from her pups, we developed a new procedure to collect mouse milk without the injection of oxytocin. This method is easy to use, low-cost ,and non-invasive. Moreover, it provides a sufficient amount of milk for use in a wide range of biological analyses.

精漿アレルギー（Human Seminal Plasma Allergy）の 1 例

精漿アレルギー（Human Seminal Plasma Allergy）の 1 例

Bioconcentration, metabolism and effects of diphenhydramine on behavioral and biochemical markers in crucian carp (Carassius auratus)

Diphenhydramine (DPH), an antihistamine used to alleviate human allergies, is widespread in aquatic environments. However, little is known about the biochemical and behavioral effects of DPH on non-target aquatic animals. In the present study, the tissue distribution, bioconcentration, metabolism, biochemical and behavioral effects were investigated in crucian carp (Carassius auratus) exposed to various concentrations of DPH (0.84, 4.23, 21.7 and 112μgL−1) for 7d. DPH can accumulate in crucian carp, and high concentrations have been observed in the liver and brain with maximum bioconcentration factors of 148 and 81.6, respectively. A portion of the absorbed DPH was metabolized by the crucian carp to N-demethyl DPH and N,N-didemethyl DPH via N-demethylation. Direct fluorimetric assay was employed to assess metabolic activity, while oxidative stress and neurotransmission biomarkers were determined by Diagnostic Reagent Kits. DPH was found to increase hepatic 7-ethoxyresorufin O-deethylase activity in crucian carp with maximal induction of 119%. Concerning the oxidative stress status, DPH significantly inhibited superoxide dismutase (SOD, 37–58%) and glutathione S-transferase (GST, 43–65%) activities and led to a significant increase in malondialdehyde (MDA, 67–140%) levels and catalase (CAT, 38–143%) and glutathione peroxidase (GPx, 39–189%) activities in fish liver. Brain acetylcholinesterase activity was also induced in DPH-exposed crucian carp with maximal induction of 174%. In addition, shoaling was significantly enhanced, while swimming activity and feeding rates were markedly suppressed at DPH concentrations equal to or higher than 21.7μgL−1. Furthermore, significant correlations were found between oxidative stress biomarkers (SOD, CAT, GPx, GST and MDA) and behavioral parameters. Collectively, our results confirmed that DPH can accumulate and be metabolized in fish and exert a negative effect at different levels of biological organization.

The human microbiome, asthma, and allergy.

The human microbiome can be defined as the microorganisms that reside within and on our bodies and how they interact with the environment. Recent research suggests that numerous mutually beneficial interactions occur between a human and their microbiome, including those that are essential for good health. Modern microbiological detection techniques have contributed to new knowledge about microorganisms in their human environment. These findings reveal that the microbiomes of the lung and gut contribute to the pathogenesis of asthma and allergy. For example, evidence indicates that the microbiome of the gut regulates the activities of helper T cell subsets (Th1 and Th2) that affect the development of immune tolerance. Moreover, recent studies demonstrate differences between the lung microbiomes of healthy and asthmatic subjects. The hygiene and biodiversity hypotheses explain how exposure to microorganisms is associated with asthma and allergy. Although those living in developed countries are exposed to fewer and less diverse microorganisms compared with the inhabitants of developing countries, they are experiencing an increase in the incidence of asthma and allergies. Detailed analyses of the human microbiome, as are being conducted under the auspices of the Human Microbiome Project initiated in 2007, promise to contribute insights into the mechanisms and factors that cause asthma and allergy that may lead to the development of strategies to prevent and treat these diseases.

Assessing the contribution of fallen autumn leaves to airborne fungi in an urban environment

Many street trees in urban areas are deciduous and drop leaves during autumn. These leaves are a potential growing substrate for fungi, which when aerosolized and inhaled, can lead to allergy along with more serious diseases. This investigation assessed the potential contribution of fallen leaves to the diversity of airborne fungal propagules during autumn. The senescent leaves of five deciduous tree species prevalent in urban environments were subject to a manipulative experiment in which their phyllospheric fungi were aerosolized, cultured and identified. Aerosolized fungi were compared with fungi detected from direct observation of the phyllosphere. Thirty-nine fungal genera were identified across the plant species sampled, of which twenty-eight were present in corresponding air samples. Significant differences were observed amongst the fungal genera growing on the leaves of the different trees, however few differences were found in the composition of fungal spores that were aerosolized. The dominant genera that were aerosolized were: Penicillium, Cladosporium, Alternaria, Chaetomium, Botrytis and Trichothecium. Some of these fungi are known to produce allergy and other symptoms in humans. As these fungal genera have been commonly identified in autumn air samples in other studies, it is likely that the phyllospheric fungi present on deciduating leaves contribute to the aeromycota of urban areas.

What is living on your dog's skin? Characterization of the canine cutaneous mycobiota and fungal dysbiosis in canine allergic dermatitis.

To characterize the skin-associated fungal microbiota (mycobiota) in dogs, and to evaluate the influence of body site, individual dog or health status on the distribution of fungi, next-generation sequencing was performed targeting the internal transcribed spacer region. A total of 10 dogs with no history of skin disease were sampled at 10 distinct body sites consisting of haired and mucosal skin, and 8 dogs with diagnosed skin allergies were sampled at six body sites commonly affected by allergic disease. Analysis of similarities revealed that body site was not an influencing factor on membership or structure of fungal communities in healthy skin; however, the mucosal sites were significantly reduced in fungal richness. The mycobiota from body sites in healthy dogs tended to be similar within a dog, which was visualized in principle coordinates analysis (PCoA) by clustering of all sites from one dog separate from other dogs. The mycobiota of allergic skin was significantly less rich than that of healthy skin, and all sites sampled clustered by health status in PCoA. Interestingly, the most abundant fungi present on canine skin, across all body sites and health statuses, were Alternaria and Cladosporium—two of the most common fungal allergens in human environmental allergies.

A histamine-independent itch pathway is required for allergic ocular itch

Non-histaminergic TRPA1 neural pathway is required for the development of allergic ocular itch. Pharmacological inhibition of TRPA1 channel can lead to novel therapeutic strategies to treat ocular itch in severe allergic conjunctivitis.

프로바이오틱스의 기능성 향상을 위한 배양법

The functions of probiotics, particularly Lactic acid bacteria, have been studied in a range of human diseases, including cancer, infectious diseases, gastrointestinal disorders, and allergies. Among the many ben- efits associated with the consumption of probiotics, modulation of immune activity has received the most attention. This study aimed at investigating the improved immune stimulatory and stability of L. plantarum when cultivated on modified basal media supplemented with the Undaria pinnatifida co-cultured with L. plantarum. An in vitro test showed that U. pinnatifida media cultured L. plantarum is strong enough to survive in the gastric juice (gastric and bile acid). Mouse macrophage-derived cell lines RAW 264.7 was used to measured immune stimulating activity of L. plantarum. When U. pinnatifida media cultured by L. plantarum was NO and TNF-α production is significantly increased compared to basal media cultured L. plantarum. These results show that U. pinnatifida could be applied for a component for cultivation of L. plantarum. This optimized U. pinnatifida medium can be used the improving of sta- bility and immune function on production of probiotics.

Extractable low mass proteins

Human allergic reactions to peanut proteins and the associated risk of life-threatening anaphylaxis requires vigilant management of peanuts in food processing. Processed forms of peanuts with attenuated antigenicity and less severe immunogenic responses may lower the risk. Molecular subfractions of raw (UP), blanched (BP) and roasted (RP) peanuts were prepared including water-insoluble (P1), water-soluble high mass (>30kDa, P2) and water-soluble low mass (<30kDa, P3) fractions. Products were screened by measuring binding to IgG (polyclonal antibody against peanut allergen) and IgE (sera from peanut-allergic donors, RAST>3). The results showed that IgE titres were highest for total extracts of RP, particularly for P3 fractions of UP and RP, and were affected by further heating. Antigenicity was also modulated by heating in the presence of either peanut oil or non-peanut food ingredients (lactose, coconut oil). Results support several alternative methods for regulating peanut antigenicity using food processing approaches but require further substantiation in larger numbers of allergic and control donor sera.

Cutaneous exposure to agglomerates of silica nanoparticles and allergen results in IgE-biased immune response and increased sensitivity to anaphylaxis in mice

BackgroundThe skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances.ResultsRepeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen–silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles.ConclusionsOur data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-015-0095-3) contains supplementary material, which is available to authorized users.

Array of Synthetic Oligonucleotides to Generate Unique Multi-Target Artificial Positive Controls and Molecular Probe-Based Discrimination of Liposcelis Species

Several species of the genus Liposcelis are common insect pests that cause serious qualitative and quantitative losses to various stored grains and processed grain products. They also can contaminate foods, transmit pathogenic microorganisms and cause allergies in humans. The common occurrence of multi-species infestations and the fact that it is difficult to identify and discriminate Liposcelis spp. make accurate, rapid detection and discriminatory tools absolutely necessary for confirmation of their identity. In this study, PCR primers and probes specific to different Liposcelis spp. were designed based on nucleotide sequences of the cytochrome oxidase 1 (CO1) gene. Primer sets ObsCo13F/13R, PeaCo15F/14R, BosCO7F/7R, BruCo5F/5R, and DecCo11F/11R were used to specifically detect Liposcelis obscura Broadhead, Liposcelis pearmani Lienhard, Liposcelis bostrychophila Badonnel, Liposcelis brunnea Motschulsky and Liposcelis decolor (Pearman) in multiplex endpoint PCRs, which amplified products of 438-, 351-, 191-, 140-, and 87-bp, respectively. In multiplex TaqMan qPCR assays, orange, yellow, red, crimson and green channels corresponding to reporter dyes 6-ROXN, HEX, Cy5, Quasar705 and 6-FAM specifically detected L. obscura, L. brunnea, L. bostrychophila, L. pearmani and L. decolor, respectively. All developed primer and probe sets allowed specific amplification of corresponding targeted Liposcelis species. The development of multiplex endpoint PCR and multiplex TaqMan qPCR will greatly facilitate psocid identification and their management. The use of APCs will streamline and standardize PCR assays. APC will also provide the opportunity to have all positive controls in a single tube, which reduces maintenance cost and labor, but increases the accuracy and reliability of the assays. These novel methods from our study will have applications in pest management, biosecurity, quarantine, food safety, and routine diagnostics.

Do human rhinovirus infections and food allergy modify grass pollen–induced asthma hospital admissions in children?

Asthma prevalence in children has remained relatively constant in many Western countries, but hospital admissions for younger age groups have increased over time.1 Although the role of outdoor aeroallergens as triggers for asthma exacerbations requiring hospitalization in children and adolescents is complex, there is evidence that increasing concentrations of grass pollen are associated with an increased risk of asthma exacerbations in children.2 Human rhinovirus (HRV) infections are implicated in most of the serious asthma exacerbations in school-age children.3 In previous research, HRV infections and aeroallergen exposure have usually been studied independently. To our knowledge, only 1 study has examined interactions between these 2 factors,4 but lack of power prevented any meaningful interpretation...

Expression profiling of human basophils: modulation by cytokines and secretagogues.

Human basophils are an accessible participant of the human allergic reaction. There is natural variation in various functional endpoints and in signaling molecule expression but there has been only a limited effort to place this information in the context of mRNA expression profiles. This study examined the hypothesis that unique mRNA signatures could be identified during the response of human basophils to several known forms of stimulation. Highly purified human basophils were cultured in vitro and exposed to IL-3, IL-5, NGF, IL-33, IL-2, anti-IgE Ab, or FMLP and the mRNA profiles examined by microarrays. The response to IL-3 and anti-IgE Ab were examined on 2–3 time frames and the response to IL-3 examined at several concentrations. In addition, the mRNA signatures of 3 different potential phenotypes were examined. These included basophils with the so-called non-releaser phenotype, and basophils from atopic and non-atopic subjects. Given the role of IL-3 in basophil maturation and the known profound effects on mature basophil function, it was not surprising that IL-3 showed the greatest influence on the basophil transcriptome. However, it also became apparent that the act of isolating and culturing basophils was sufficient to induce a large number of changes in the transcriptome, despite high viability and recovery. These “culture-effect” changes dominated the changes in mRNA profiles induced by other stimuli. Unique signatures for anti-IgE antibody and IL-33 could be identified although the number of gene transcripts (6–30) that were unique to these two stimuli was very limited. There were no apparent unique profiles for IL-5, NGF, IL-2 or FMLP. Therefore, a potential tool for screening basophil phenotypes was limited to changes that could be induced by IL-3 (or no IL-3), IL-33 and anti-IgE Ab.

Boosting antitumor immunity through TIM1 (IRM11P.631)

Abstract The lack of co-stimulation, as well as the dominance of co-inhibition, of type 1 lymphocytes, such as CD8+ T cells and NK cells, is a principal immunosuppressive mechanism in the tumor microenvironment. Conversion of the tumor immunosuppressive microenvironment to one that favors cancer-eradicating immune responses is therefore a goal for the development of more effective cancer immunotherapy. Targeting co-stimulatory pathways represents one attractive therapeutic strategy. T cell Ig mucin (TIM) proteins are structurally related to type I membrane glycoproteins. Previous studies have shown that TIM-1 is highly expressed on activated CD4+ T cells, facilitates the activation of Th1 cells, Th17 cells, and Th2 cells, and is implicated in the pathogenesis of human allergy and autoimmune diseases. These data support an important role for TIM-1 in regulating CD4+ T cell function. However, the role for TIM-1 in CD8+ T cell- or NK cell-mediated immune responses, including antitumor immune responses, is unknown. Here we showed that tumoral expression of antitumor cytokines such as IL-12 and IL-33 upregulated TIM-1 on tumor-infiltrating CD8+ T cells and NK cells. In addition, we demonstrated that TIM1 mAbs greatly inhibited tumor growth, resulting in greatly elevated cellular immune responses against tumor. The in-depth mechanistic insights and implication in tumor immunity are gained by our studies. Our study establishes TIM-1 as a potential target for enhancing antitumor immunity.

FIRST REPORT OF TRICHOCONIELLA PADWICKII CAUSING LEAF SPOT DISEASE ON PARTHENIUM WEED

Parthenium hysterophorus is an annual or ephemeral weed causing great damage to grassland ecosystems, but also allergy and dermatitis in humans and livestock. Since the use of fungal pathogens has been suggested as a most efficient biocontrol method, a survey was conducted in 2012-2014 in the Haryana state (India), during which dark brown to black marginal spots were observed on parthenium leaves. These lesions were initially round pinpoints that enlarged and coalesced causing a premature defoliation. From symptomatic leaves collected from different areas, surface-sterilized in 70% ethanol and placed on PDA, a fungus was isolated showing an initially whitish brown aerial mycelium that turned orange- brown to purple black (Aneja et al., 2000). Conidiophores were brown, straight to geniculate (160 x 5.0-9.3 μm), bearing obclavate, rostrate, pale to golden brown 71-103×16.4-23.6 μm conidia, smooth to minutely verruculose, with 5-9 transverse but no longitudinal septa, singly or in chains of two. The conidial beak (50-172 x 1.4-3.1 μm) was hyaline, filiform, septate, straight to geniculate, sometimes swollen at the apex, often much longer than the spore body. Based on these characteristics, the fungus was identified as Trichoconiella padwickii (Ellis, 1971), as confirmed by the International Mycological Institute (IMI accession no. 502783). Pathogenicity was proven by placing seven-day-old mycelial plugs (5 mm) on detached parthenium leaves that reacted with spots from which T. padwickii was re-isolated. The ITS rDNA sequence analysed using the FASTA algorithm shared 100% nucleotide similarity to six unpublished ITS sequences from Alternaria padwickii (current name T. padwickii). This pathogen has previously been reported on rice, millet, sorghum, eucalyptus and various grasses but, to our knowledge, this is the first report on P. hysterophorus.

Antihelmintic effects of nutmeg (Myristica fragans) on Anisakis simplex L3 larvae obtained from Micromesistius potassou

Anisakis simplex is a foodborne pathogen that can produce human infections and allergic reactions due to the high consumption of raw fish. The seeds of Myristica fragans (Myristicaceae), popularly known as nutmeg, are worldwide used as a culinary spice due to its flavour and properties in food preservation. A nutmeg extract was prepared, analyzed, screened for cytotoxicity and tested against Anisakis simplex L3 larvae. In order to detect the biologically active constituents of the extract, myristicin was tested on the larvae. An acetylcholinesterase inhibition bioassay was also carried out to investigate the antihelmintic mechanism of action. Our results demonstrate that nutmeg exerts antihelmintic effects on Anisakis simplex, being myristicin one of the active compounds. The extract induced a high rate of dead anisakis at concentrations between 0.5 and 0.7 mg/ml without being considered cytotoxic; however, an inhibition of acetylcholinesterase was discarded as the molecular mechanism involved in the activity.

Proinflammatory Environmental Exposures in Asthma

Asthma is a chronic inflammatory disease that affects over 35 million people in the United States, and is a leading cause of hospitalization in children. While asthma‐causing allergens like fungi, mites, and insects represent biologically diverse organisms, they have some biological similarities that may underlie their potential to cause asthma. One of these shared biological features is the production of chitin. Studies have shown that chitin impacts lung function through the innate immune system. There are no available chitin assays for assessing environmental samples. Creation of a quantitative assay for chitin is complicated because it is a modified polysaccharide and not a protein. This makes it difficult to make antibodies that will specifically recognize it. Chitin is also poorly soluble in water and many standard solvents, which makes developing adequate standards challengingAfter successfully creating a chitin quantification assay with a detection limit of about 20ng/mg dust and validating commercially available assays for endotoxins and lipopolysaccharides, we acquired 387 household dust samples from the Inner‐City Anti‐IgE Therapy for Asthma (ICATA) clinical trial and quantified MAMPS like chitin, endotoxins and lipopolysaccharides in those samples. Quantifying chitin, endotoxins and glucans in household dust samples gave us a better understanding of the microbiome profile in those samples. Overall, this study contributes to our understanding of the mechanisms in human asthma and allergy. It also has the potential to improve existing techniques in the treatment and prevention of a disease that affects millions of people worldwide.

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization.

Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans.

Blockade of oral tolerance to ovalbumin in mice by silver nanoparticles.

The authors investigated the effect of silver nanoparticles (Ag NPs) on oral tolerance to dietary antigen ovalbumin (OVA) in mice. Ag NPs were orally administered for 7 days before feeding of OVA and the immunological responses were assayed. Polyvinyl pyrrolidone-coated Ag NPs (Ag NPs-PVP) were found to block the induction of oral tolerance to OVA. The physicochemical properties of the three kinds of Ag NPs were assessed and silver ions were found to inhibit the induction of oral tolerance, which might be the dominating factor in the blockade of oral tolerance by Ag NPs-PVP. Ag NPs with certain physicochemical properties can block oral tolerance to dietary antigen that may induce food allergy in humans.