Occupational Animal Allergy.

PURPOSE OF REVIEW: This review explores animal allergen exposure in research laboratories and other work settings, focusing on causes and prevention. RECENT FINDINGS: (1) Consistent with the hygiene hypothesis, there is new evidence that early childhood exposure to pets produces changes in the gut microbiome that likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal bites occurs more frequently than suggested by prior literature. (3) Animal allergens represent an occupational hazard in a wide variety of work settings ranging from fields that work with animals to public settings like schools and public transportation where allergens are brought into or are present in the workplace. Exposure to animal allergens can result in allergy, asthma, and anaphylaxis. Animal allergy has been most studied in the research laboratory setting, where exposure reduction can prevent the development of allergy. Similar prevention approaches need to be considered for other animal work environments and in all settings where animal allergens are present.

Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation.

BACKGROUND Migration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using pantethine, a pleiotropic natural compound which has been recently shown to down-regulate chemokine-driven T cell migration. MATERIAL AND METHODS Mice were sensitized to the Leishmania LACK antigen, then treated or not treated with pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals, cells in the bronchoalveolar lavage were analyzed and inflammatory parameters were determined to evaluate inflammation seriousness. RESULTS As compared to untreated animals, pantethine-treated animals displayed a moderated response to the allergen, as documented by decreased infiltration of inflammatory cells (all types), in addition to reduced levels of lung Th2 cytokines and circulating LACK-specific IgE. CONCLUSIONS These data reveal the potential therapeutic importance of pantethine to moderate allergic asthma pathology. The compound has been previously shown to exert a broad range of protective activity in animals and in humans, with few or no adverse effects.

Estimating the abundance of airborne pollen and fungal spores at variable elevations using an aircraft: how high can they fly?

Airborne pollen and fungal spores are monitored mainly in highly populated, urban environments, for allergy prevention purposes. However, their sources can frequently be located outside cities' fringes with more vegetation. So as to shed light to this paradox, we investigated the diversity and abundance of airborne pollen and fungal spores at various environmental regimes. We monitored pollen and spores using an aircraft and a car, at elevations from sea level to 2,000 m above ground, in the region of Thesssaloniki, Greece. We found a total of 24 pollen types and more than 15 spore types. Pollen and spores were detected throughout the elevational transect. Lower elevations exhibited higher pollen concentrations in only half of plant taxa and higher fungal spore concentrations in only Ustilago. Pinaceae and Quercus pollen were the most abundant recorded by airplane (>54% of the total). Poaceae pollen were the most abundant via car measurements (>77% of the total). Cladosporium and Alternaria spores were the most abundant in all cases (aircraft: >69% and >17%, car: >45% and >27%, respectively). We conclude that pollen and fungal spores can be diverse and abundant even outside the main source area, evidently because of long-distance transport incidents.

Professional Music Training and Novel Word Learning: From Faster Semantic Encoding to Longer-lasting Word Representations.

On the basis of previous results showing that music training positively influences different aspects of speech perception and cognition, the aim of this series of experiments was to test the hypothesis that adult professional musicians would learn the meaning of novel words through picture-word associations more efficiently than controls without music training (i.e., fewer errors and faster RTs). We also expected musicians to show faster changes in brain electrical activity than controls, in particular regarding the N400 component that develops with word learning. In line with these hypotheses, musicians outperformed controls in the most difficult semantic task. Moreover, although a frontally distributed N400 component developed in both groups of participants after only a few minutes of novel word learning, in musicians this frontal distribution rapidly shifted to parietal scalp sites, as typically found for the N400 elicited by known words. Finally, musicians showed evidence for better long-term memory for novel words 5 months after the main experimental session. Results are discussed in terms of cascading effects from enhanced perception to memory as well as in terms of multifaceted improvements of cognitive processing due to music training. To our knowledge, this is the first report showing that music training influences semantic aspects of language processing in adults. These results open new perspectives for education in showing that early music training can facilitate later foreign language learning. Moreover, the design used in the present experiment can help to specify the stages of word learning that are impaired in children and adults with word learning difficulties.

ALL2, a Homologue of ALL1, Has a Distinct Role in Regulating pH Homeostasis in the Pathogen Cryptococcus neoformans.

Cryptococcus neoformans is a facultative intracellular fungal pathogen that has a polysaccharide capsule and causes life-threatening meningoencephalitis. Its capsule, as well as its ability to survive in the acidic environment of the phagolysosome, contributes to the pathogen's resilience in the host environment. Previously, we reported that downregulation of allergen 1 (ALL1) results in the secretion of a shorter, more viscous exopolysaccharide with less branching and structural complexity, as well as altered iron homeostasis. Now, we report on a homologous coregulated gene, allergen 2 (ALL2). ALL2's function was characterized by generating null mutants in C. neoformans. In contrast to ALL1, loss of ALL2 attenuated virulence in the pulmonary infection model. The all2Δ mutant shed a less viscous exopolysaccharide and exhibited higher sensitivity to hydrogen peroxide than the wild type, and as a result, the all2Δ mutant was more resistant to macrophage-mediated killing. Transcriptome analysis further supported the distinct function of these two genes. Unlike ALL1's involvement in iron homeostasis, we now present data on ALL2's unique function in maintaining intracellular pH in low-pH conditions. Thus, our data highlight that C. neoformans, a human-pathogenic basidiomycete, has evolved a unique set of virulence-associated genes that contributes to its resilience in the human niche.

Effect of nitrogen dioxide and sulfur dioxide on viability and morphology of oak pollen.

BACKGROUND: Nitrogen dioxide (NO2) and sulfur dioxide (SO2) generated by excessive coal combustion and motor vehicle emissions are major air pollutants in the large cities of China. The objective of our study was to determine the effects of the exposure of oak pollens (Quercusmongolica) to several concentrations of NO2 or SO2. METHODS: Pollen grains were exposed to 0.5 ppm to 5.0 ppm NO2 or SO2 for 4 hours and assessed for morphological damage by field emission scanning electron microscopy and for viability using the trypan blue stain. Morphological changes in pollen grains were also examined after contact with acid solutions at pH 4.0 to pH 7.0. RESULTS: Exposure to NO2 or SO2 significantly damaged pollen grains at all concentrations investigated, compared to exposure to air; with exposure to concentrations of 0.5 ppm to 2 ppm resulting in fissures or complete breaks in the exine and a concentration of 5 ppm resulting in complete breakdown and release of pollen cytoplasmic granules. Significantly greater amounts of pollen grain were damaged after exposure to SO2 (15.5-20.4%) than after exposure to NO2 (7.1-14.7%). Similarly, exposure to NO2 or SO2 significantly decreased the viability of pollen grains, compared with exposure to air; with SO2 being slightly more detrimental than NO2. Exposure to acid solutions also induced pollen damage, which appeared to be pH-dependent (from 24.6% at pH 6.0 to 55.8% at pH 4.0; compared to 3.8% at pH 7.0). CONCLUSION: Short-term exposure of oak pollen to high concentrations of SO2 or NO2 significantly increases their fragility and disruption, leading to subsequent release of pollen cytoplasmic granules into the atmosphere. These results suggest that heightened air pollution during the oak pollen season may possibly increase the incidence of allergic airway disease in sensitized individuals by facilitating the bioavailability of airborne pollen allergens.

Phenological changes in olive (Ola europaea L.) reproductive cycle in southern Spain due to climate change.

INTRODUCTION: Modifications of crop species phenology due to a changing environment are of interest because of their impact on fruit set and final harvest. Pre-flowering and flowering phenophases in olive groves at different sites of southern Spain were examined, in order to chart potential trends and determine major correlations with weather-related parameters, especially temperature and water availability. The high prevalence of olive pollen allergy in the Mediterranean population makes this study highly relevant. MATERIALS AND METHODS: Ten sites in Cordoba province (Spain) during a 17-year period (1996-2012). BBCH phenology scale. Meteorological data from 1960 were analyzed; data from 1996 included on modeling analysis. Linear Mixed Models (LMMs) were developed, combining phenological and meteorological data. RESULTS: Since 1960, local spring temperatures have increased 1.5ºC, the number of spring rainfall days has fallen 11 days, total rainfall has declined 150 mm. Despite phenological differences between sites, attributable to altitude, phenological development during the season followed a similar pattern. Flowering dates advanced 2 days, while inflorescence emergence was delayed 24 days. Trend slopes revealed differences, an earlier period (1996-2002) with a sharp flowering advance of 15 days, and a later period (2003-2012) characterized by a gradual advance and a high bud emergence delay of 22 days. CONCLUSIONS: LMMs was revealed as an appropriate technique for phenology behaviour analysis displaying both fixed and random interactions. Cultivars grown in the study province are adapted to climate with a synchronized response, although climate change is affecting theolive reproductive cycle in southern Spain; therefore, the timing of pollen release, with subsequent consequences on allergic population as phenological changes, could have impacts on flowering period and pollen production. Further investigation is required of the implications for crop production in Mediterranean ecosystems.

A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses.

RATIONALE: Effective antiinflammatory therapies are needed for the treatment of asthma, but preferably without the systemic adverse effects of glucocorticosteroids. OBJECTIVES: We evaluated the effect of an inhaled nonsteroidal glucocorticoid receptor agonist, AZD5423, on allergen-induced responses. METHODS: Twenty subjects with mild allergic asthma were randomized to receive 7 days of treatment with nebulized AZD5423 (75 or 300 µg) once daily, budesonide 200 µg twice daily via Turbuhaler, or placebo in a double-blind, four-period, crossover design study. Allergen challenge was performed on Day 6. MEASUREMENTS AND MAIN RESULTS: FEV1 was measured repeatedly for 7 hours after allergen challenge for early and late asthmatic responses. Sputum inflammatory cells was measured before and at 7 and 24 hours after allergen challenge, and methacholine airway responsiveness was measured before and 24 hours after allergen challenge. AZD5423 significantly attenuated the fall in FEV1 during the late asthmatic response (both doses led to an 8.7% fall) versus placebo (14% fall) (P < 0.05) with no effect of budesonide (12.5% fall) versus placebo (P > 0.05). There was no effect on the fall in FEV1 during early asthmatic response. AZD5423 300 and 75 µg significantly attenuated allergen-induced sputum eosinophilia by 63 and 61% at 7 hours, respectively, and by 46 and 34% at 24 hours after allergen challenge, respectively, versus placebo (all P < 0.05). Budesonide did not reduce allergen-induced sputum eosinophilia versus placebo. AZD5423 at 300 µg significantly attenuated allergen-induced airway hyperresponsiveness at 24 hours after allergen challenge versus placebo (P < 0.05). Both doses of AZD5423 were well tolerated. CONCLUSIONS: Seven-day treatment with inhalation of the nonsteroidal glucocorticoid receptor agonist AZD5423 effectively reduced allergen-induced responses in subjects with mild allergic asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01225549).

[Clustering Sugi-pollen dispersal patterns for the past 26 years].

BACKGROUND: Pollinosis caused by the pollen of Sugi (Cryptopmeria japonica) trees is the most significant allergic disease occurring in the spring in Japan. For pollinosis patients and medical staff, it is important to know when the pollen dispersion would reach maximum or when the pollen count would decrease as well as knowing what would the total density of pollen grains be. These sorts of information could be useful for the purpose of disease prevention and deciding on the therapeutic regimen. In this study, we presented the sugi-dispersal patterns and cited several examples of the dispersal pattern. METHODS: Airborne pollen grains were collected using a Durham sampler. Total annual pollen counts/cm2 were examined. The sugi-dispersal patterns were classified into several groups by cluster analysis using variables of ten days pollen counts distribution from February to April for the past 26 years. (1987-2012). RESULT: The annual pollen count revealed an alternate rhythm consisting of an "on" year (high pollen count) and an "off" year (low pollen count). The results of the cluster analysis showed eleven off-years classified as one group (group 1), and fifteen on-years classified into three groups (groups 2A, 2B, and 2C). The dispersal pattern in group 1 was almost symmetrical with the pollen count rapidly decreasing until late-March. On the other hand, the patterns in group 2 were asymmetrical. In group 2A and 2B a high rate of dispersion was indicated after maximum dispersion, whereas in group 2C the high rate of dispersion was indicated before maximum dispersion. In group 2A, a major dispersion of almost 3000 grains was noted in late-March, and immediately proceeded to the cypress (Chamaecyparis) pollen season without any decrease seen in pollen dispersion. The periods of dispersion of over 10 pollen grains/cm2 per day were 38, 47, 47 and 51 days in groups 1, 2A, 2B and 2C, respectively. That in group 2 was significantly longer than that in group 1, but there was no significant differences between groups 2A, 2B and 2C. CONCLUSION: In conclusion, in the dispersal pattern whereby a major dispersion was seen in late-March and proceeded to the cypress pollen season such as in group 2A, patients' symptoms might be prolonged or be more serious. This new concept of dispersal pattern could very well be useful for clinical management of pollinosis.

House dust mite interactions with airway epithelium: role in allergic airway inflammation.

House dust mite (HDM) allergens are the most prevalent allergens associated with asthma and rhinitis around the world. The mechanisms of allergic sensitization and allergic airway inflammation after exposure to HDM have been studied extensively, but many questions remain unanswered. Airway epithelial cells are the first line of defense against external antigens and are considered an important player in the development of allergic airway inflammation. Both genetic susceptibility to allergic sensitization and HDM composition play decisive roles in the outcome of HDM-epithelium interactions, especially regarding airway epithelial dysfunction and allergic inflammation. Interactions between HDM and the airway epithelium have consequences for both development of allergy and asthma and development of allergic airway inflammation. This review will describe in detail these interactions and will identify issues that require more study.

Wind-pollination and the roles of pollen allergenic proteins.

Over the past few decades, there has been an explosion of understanding of the molecular nature of major allergens contained within pollens from the most important allergenic plant species. Most major allergens belong to only a few protein families. Protein characteristics, cross-reactivity, structures, and IgE binding epitopes have been determined for several allergens. These efforts have led to significant improvements in specific immunotherapy, yet there has been little discussion about the physiological functions of these proteins. Even with large amounts of available information about allergenic proteins from pollens, the incidence of pollen allergy continuously increases worldwide. The reason for this increase is unclear and is most likely due to a combination of factors. One important culprit might be a change in the pollen itself. Knowledge about pollen biology and how pollen is changing as a result of more extreme environmental conditions might improve our understanding of the disease. This review focuses on the characteristics of plants producing allergenic pollens that are relevant to pollen allergy, including the phylogenetic relationships, pollen dispersal distances, amounts of pollen produced, amounts of protein in each type of pollen, and how allergenic proteins are released from pollens. In addition, the physiological roles of major allergenic protein families will be discussed to help us understand why some of these proteins become allergens and why GMO plants with hypoallergenic pollens may not be successful.

Design of a heterotetravalent synthetic allergen that reflects epitope heterogeneity and IgE antibody variability to study mast cell degranulation.

The present paper describes the design of a HtTA (heterotetravalent allergen) as a multi-component experimental system that enables an integrative approach to study mast cell degranulation. The HtTA design allows presentation of two distinct haptens, each with a valency of 2, thereby better reflecting the complexity of natural allergens by displaying epitope heterogeneity and IgE antibody variability. Using the HtTA design, synthetic allergens HtTA-1 and HtTA-2 were synthesized to model a combination of epitope/IgE affinities. HtTA-1 presented DNP (2,4-dinitrophenyl) and dansyl haptens (Kd=22 and 54 nM for IgEDNP and IgEdansyl respectively) and HtTA-2 presented dansyl and the weak-affinity DNP-Pro (DNP-proline) haptens (Kd=550 nM for IgEDNP). Both HtTAs effectively induced degranulation when mast cells were primed with both IgEDNP and IgEdansyl antibodies. Interestingly tetravalent DNP-Pro or bivalent dansyl were insufficient in stimulating a degranulation response, illustrating the significance of valency, affinity and synergy in allergen-IgE interactions. Importantly, maximum degranulation with both HtTA-1 and HtTA-2 was observed when only 50% of the mast cell-bound IgEs were hapten-specific (25% IgEdansyl and 25% IgEDNP). Taken together, results of the present study establish the HtTA system as a physiologically relevant experimental model and demonstrates its utility in elucidating critical mechanisms of mast cell degranulation.

Antibodies generated against conserved antigens expressed by bacteria and allergen-bearing fungi suppress airway disease.

There has been a sharp rise in allergic asthma and asthma-related deaths in the developed world, in contrast to many childhood illnesses that have been reduced or eliminated. The hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. We demonstrate that Abs generated against conserved bacterial polysaccharides are reactive with and dampen the immune response against chitin and Aspergillus fumigatus. A reduction in Ag uptake, cell influx, cell activation, and cytokine production occurred in the presence of anti-polysaccharide Abs, resulting in a striking decrease in the severity of allergic airway disease in mice. Overall, our results suggest that Ag exposure--derived from environmental sources, self-antigens, or vaccination--during the neonatal period has dramatic effects on the adult Ab response and modifies the development of allergic airway disease.

Ragweed pollen observed in Turkey: detection of sources using back trajectory models.

This paper discusses the pollen season and the source apportionment of ragweed (Ambrosia) grains detected in the atmosphere of Istanbul, Turkey. The dynamic migration of this invasive taxon is a serious environmental issue. Ragweed pollen is highly allergenic and causes sensitization in patients at low concentrations. At present, there is no floristic evidence of this taxon in the region. Aerobiological records presented here, though, indicate a local source. Moreover, we argue that ragweed pollen comes from distant sources through air mass movements. The analysis concerns the ragweed season 2007. Pollens were sampled with a Burkard trap and identified at a magnification of 400 ×. Grains were counted on 12 transverse traverses to estimate bi-hourly changes in concentrations. The peak day was on August 28 with 20 grainsm(-3). Ragweed was observed on 22 days during August and September 2007. On all days, except one, the daily average concentration was below 10 grainsm(-3). Diurnal bi-hourly ragweed concentrations reached a maximum at 11:00 EET. Relatively high concentrations were observed between 21:00 and 01:00 EET. This allowed for the assumption of a local and a remote ragweed pollen source. We used HYSPLIT backward trajectory ensembles to identify possible sources on peak day. A frequency analysis of back trajectories covering the entire ragweed season followed. Firstly, possible local sources were the Istanbul Province and Turkish Thrace; secondly, a likely over-regional source was Bulgaria; and lastly, remote sources of ragweed pollen were the Ukraine, the Russian coastal region of the Black Sea and Moldova. This study provides evidence that pollens detected on our receptor site stem from combined local and remote origins.

In vitro exposure of Acer negundo pollen to atmospheric levels of SO2 and NO2: effects on allergenicity and germination.

In the last years, a rising trend of pollen allergies in urban areas has been attributed to atmospheric pollution. In this work, we investigated the effects of SO(2) and NO(2) on the protein content, allergenicity, and germination rate of Acer negundo pollen. A novel environmental chamber was assembled to exposure pollen samples with SO(2) or NO(2) at two different levels: just below and two times the atmospheric hour-limit value acceptable for human health protection in Europe. Results showed that protein content was lower in SO(2)-exposed pollen samples and slightly higher in NO(2)-exposed pollen compared to the control sample. No different polypeptide profiles were revealed by SDS-PAGE between exposed and nonexposed pollen, but the immunodetection assays indicated higher IgE recognition by all sera of sensitized patients to Acer negundo pollen extracts in all exposed samples in comparison to the nonexposed samples. A decrease in the germination rate of exposed in contrast to nonexposed pollen was verified, which was more pronounced for NO(2)-exposed samples. Our results indicated that in urban areas, concentrations of SO(2) and NO(2) below the limits established for human protection can indirectly aggravate pollen allergy on predisposed individuals and affect plant reproduction.

Inducible CD4+LAP+Foxp3- regulatory T cells suppress allergic inflammation.

Regulatory T cells (Tregs) play a critical role in the maintenance of airway tolerance. We report that inhaled soluble Ag induces adaptive Foxp3(+) Tregs, as well as a regulatory population of CD4(+) T cells in the lungs and lung-draining lymph nodes that express latency-associated peptide (LAP) on their cell surface but do not express Foxp3. Blocking the cytokine IL-10 or TGF-ß prevented the generation of LAP(+) Tregs and Foxp3(+) Tregs in vivo, and the LAP(+) Tregs could also be generated concomitantly with Foxp3(+) Tregs in vitro by culturing naive CD4(+) T cells with Ag and exogenous TGF-ß. The LAP(+) Tregs strongly suppressed naive CD4(+) T cell proliferation, and transfer of sorted OVA-specific LAP(+) Tregs in vivo inhibited allergic eosinophilia and Th2 cytokine expression in the lung, either when present at the time of Th2 sensitization or when injected after Th2 cells were formed. Furthermore, inflammatory innate stimuli from house dust mite extract, nucleotide-binding oligomerization domain containing 2 ligand, and LPS, which are sufficient for blocking airway tolerance, strongly decreased the induction of LAP(+) Tregs. Taken together, we concluded that inducible Ag-specific LAP(+) Tregs can suppress asthmatic lung inflammation and constitute a mediator of airway tolerance together with Foxp3(+) Tregs.

Serum amyloid A activates the NLRP3 inflammasome and promotes Th17 allergic asthma in mice.

IL-1ß is a cytokine critical to several inflammatory diseases in which pathogenic Th17 responses are implicated. Activation of the NLRP3 inflammasome by microbial and environmental stimuli can enable the caspase-1-dependent processing and secretion of IL-1ß. The acute-phase protein serum amyloid A (SAA) is highly induced during inflammatory responses, wherein it participates in systemic modulation of innate and adaptive immune responses. Elevated levels of IL-1ß, SAA, and IL-17 are present in subjects with severe allergic asthma, yet the mechanistic relationship among these mediators has yet to be identified. In this study, we demonstrate that Saa3 is expressed in the lungs of mice exposed to several mixed Th2/Th17-polarizing allergic sensitization regimens. SAA instillation into the lungs elicits robust TLR2-, MyD88-, and IL-1-dependent pulmonary neutrophilic inflammation. Furthermore, SAA drives production of IL-1α, IL-1ß, IL-6, IL-23, and PGE(2), causes dendritic cell (DC) maturation, and requires TLR2, MyD88, and the NLRP3 inflammasome for secretion of IL-1ß by DCs and macrophages. CD4(+) T cells polyclonally stimulated in the presence of conditioned media from SAA-exposed DCs produced IL-17, and the capacity of polyclonally stimulated splenocytes to secrete IL-17 is dependent upon IL-1, TLR2, and the NLRP3 inflammasome. Additionally, in a model of allergic airway inflammation, administration of SAA to the lungs functions as an adjuvant to sensitize mice to inhaled OVA, resulting in leukocyte influx after Ag challenge and a predominance of IL-17 production from restimulated splenocytes that is dependent upon IL-1R signaling.

The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses.

The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca(2+) concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y(2) receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma.

The mannose receptor mediates the uptake of diverse native allergens by dendritic cells and determines allergen-induced T cell polarization through modulation of IDO activity.

The mannose receptor (MR) is a C-type lectin expressed by dendritic cells (DCs). We have investigated the ability of MR to recognize glycosylated allergens. Using a gene silencing strategy, we have specifically inhibited the expression of MR on human monocyte-derived DCs. We show that MR mediates internalization of diverse allergens from mite (Der p 1 and Der p 2), dog (Can f 1), cockroach (Bla g 2), and peanut (Ara h 1) through their carbohydrate moieties. All of these allergens bind to the C-type lectin-like carbohydrate recognition domains 4-7 of MR. We have also assessed the contribution of MR to T cell polarization after allergen exposure. We show that silencing MR expression on monocyte-derived DCs reverses the Th2 cell polarization bias, driven by Der p 1 allergen exposure, through upregulation of IDO activity. In conclusion, our work demonstrates a major role for MR in glycoallergen recognition and in the development of Th2 responses.

Strain differences influence N-methyl-D-aspartate receptor subunit gene expression in the olfactory bulb of an allergic mouse model following toluene exposure.

OBJECTIVE: Genetic variation is a causative factor in differing sensitivities to environmental chemicals. The present study explored whether differences in mouse strains influence N-methyl-D-aspartate (NMDA) receptor expression in the olfactory bulb after low-level toluene exposure. METHODS: Ten-week-old male C3H/HeN (H-2(k)), BALB/c (H-2(d)) and C57BL/10 (H-2(b)) mice were exposed to 0, 5, 50 or 500 ppm of toluene for 6 h per day, 5 days per week for 6 weeks. Because individuals with allergic disease are more susceptible to volatile organic compound exposure, the animals of each strain were divided into 2 main groups, a non-allergy (NAG) group and an allergy (AG) group. The AG groups were stimulated with ovalbumin before toluene exposure. The mRNA levels of NMDA receptor subunits (NR1, NR2A and NR2B) in the olfactory bulbs of the NAG and AG groups were examined using real-time RT-PCR. RESULTS: In C3H/HeN mice, the expression levels of NR1 and NR2B mRNA decreased significantly in the AG group exposed to 500 ppm of toluene; in the NAG group, however, the NR2A mRNA level increased significantly in mice exposed to 50 ppm while the NR2A and NR2B mRNA levels decreased significantly in mice exposed to 500 ppm of toluene. No significant changes were observed in the NAG groups of BALB/c or C57BL/10 mice. However, in the BALB/c mice, the mRNA levels of NR1, NR2A and NR2B decreased significantly in the AG group exposed to 500 ppm of toluene. CONCLUSION: Mammalian strain differences in NMDA receptor expression after allergic stimulation can be observed in the mouse olfactory bulb after toluene exposure.