-
International Immunopharmacology Jun 2024Airway epithelial barrier dysfunction has been proved to contribute to the development of type 2 inflammation of asthma. Interleukin (IL)-37 is a negative regulator of...
BACKGROUND
Airway epithelial barrier dysfunction has been proved to contribute to the development of type 2 inflammation of asthma. Interleukin (IL)-37 is a negative regulator of immune responses and allergic airway inflammation. However, whether IL-37 has any effect on airway epithelial barrier has been unknown.
METHODS
We evaluated the role of IL-37 in both mouse model and cultured 16HBE cells. Histology and ELISA assays were used to evaluate airway inflammation. FITC-dextran permeability assay was used to evaluate the airway epithelial barrier function. Immunofluorescence, western blot and quantitative Real-Time PCR (RT-PCR) were used to evaluate the distribution and expression of tight junction proteins. RT-PCR and Ca fluorescence measurement were used to evaluate the mRNA expression and activity of store-operated calcium entry (SOCE).
RESULTS
IL-37 inhibited house dust mite (HDM)-induced airway inflammation and decreased the levels of IgE in serum and type 2 cytokines in bronchoalveolar lavage fluid (BALF) compared to asthmatic mice. IL-37 protected against HDM-induced airway epithelial barrier dysfunction, including reduced leakage of FITC-dextran, enhanced expression of TJ proteins, and restored the membrane distribution of TJ proteins. Moreover, IL-37 decreased the level of IL-33 in the BALF of asthmatic mice and the supernatants of HDM-treated 16HBE cells. IL-37 decreased the peak level of Ca fluorescence induced by thapsigargin and HDM, and inhibited the mRNA expression of Orai1, suggesting an inhibiting effect of IL-37 on SOCE in airway epithelial cells.
CONCLUSION
IL-37 plays a protective role in airway inflammation and HDM-induced airway epithelial barrier dysfunction by inhibiting SOCE.
PubMed: 38941668
DOI: 10.1016/j.intimp.2024.112525 -
Vaccines Jun 2024Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens...
Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs' pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine.
PubMed: 38932349
DOI: 10.3390/vaccines12060620 -
Viruses Jun 2024Honey bees () play a crucial role in agriculture through their pollination activities. However, they have faced significant health challenges over the past decades that...
Honey bees () play a crucial role in agriculture through their pollination activities. However, they have faced significant health challenges over the past decades that can limit colony performance and even lead to collapse. A primary culprit is the parasitic mite , known for transmitting harmful bee viruses. Among these viruses is deformed wing virus (DWV), which impacts bee pupae during their development, resulting in either pupal demise or in the emergence of crippled adult bees. In this study, we focused on DWV master variant B. DWV-B prevalence has risen sharply in recent decades and appears to be outcompeting variant A of DWV. We generated a molecular clone of a typical DWV-B strain to compare it with our established DWV-A clone, examining RNA replication, protein expression, and virulence. Initially, we analyzed the genome using RACE-PCR and RT-PCR techniques. Subsequently, we conducted full-genome RT-PCR and inserted the complete viral cDNA into a bacterial plasmid backbone. Phylogenetic comparisons with available full-length sequences were performed, followed by functional analyses using a live bee pupae model. Upon the transfection of in vitro-transcribed RNA, bee pupae exhibited symptoms of DWV infection, with detectable viral protein expression and stable RNA replication observed in subsequent virus passages. The DWV-B clone displayed a lower virulence compared to the DWV-A clone after the transfection of synthetic RNA, as evidenced by a reduced pupal mortality rate of only 20% compared to 80% in the case of DWV-A and a lack of malformations in 50% of the emerging bees. Comparable results were observed in experiments with low infection doses of the passaged virus clones. In these tests, 90% of bees infected with DWV-B showed no clinical symptoms, while 100% of pupae infected with DWV-A died. However, at high infection doses, both DWV-A and DWV-B caused mortality rates exceeding 90%. Taken together, we have generated an authentic virus clone of DWV-B and characterized it in animal experiments.
Topics: Animals; Bees; RNA Viruses; Phylogeny; Genome, Viral; Virus Replication; Pupa; Virulence; Varroidae; RNA, Viral
PubMed: 38932270
DOI: 10.3390/v16060980 -
Sensors (Basel, Switzerland) Jun 2024Varroa mites, scientifically identified as , pose a significant threat to beekeeping and cause one of the most destructive diseases affecting honey bee populations....
Varroa mites, scientifically identified as , pose a significant threat to beekeeping and cause one of the most destructive diseases affecting honey bee populations. These parasites attach to bees, feeding on their fat tissue, weakening their immune systems, reducing their lifespans, and even causing colony collapse. They also feed during the pre-imaginal stages of the honey bee in brood cells. Given the critical role of honey bees in pollination and the global food supply, controlling Varroa mites is imperative. One of the most common methods used to evaluate the level of Varroa mite infestation in a bee colony is to count all the mites that fall onto sticky boards placed at the bottom of a colony. However, this is usually a manual process that takes a considerable amount of time. This work proposes a deep learning approach for locating and counting Varroa mites using images of the sticky boards taken by smartphone cameras. To this end, a new realistic dataset has been built: it includes images containing numerous artifacts and blurred parts, which makes the task challenging. After testing various architectures (mainly based on two-stage detectors with feature pyramid networks), combination of hyperparameters and some image enhancement techniques, we have obtained a system that achieves a mean average precision (mAP) metric of 0.9073 on the validation set.
Topics: Animals; Varroidae; Bees; Deep Learning; Software; Mite Infestations; Beekeeping; Image Processing, Computer-Assisted
PubMed: 38931612
DOI: 10.3390/s24123828 -
Microorganisms May 2024(1) Background: The mycophagous mite, , was found to feed on entomopathogenic fungi (EPF) in our previous experiments, which seriously impacted the culture and...
(1) Background: The mycophagous mite, , was found to feed on entomopathogenic fungi (EPF) in our previous experiments, which seriously impacted the culture and preservation of fungal strains. Therefore, it is necessary to investigate the biological characteristics of the occurrence and damage to EPF. (2) Methods: The mite's growth and development and feeding preference were surveyed by comparative culture and observation; also, optical and electronic microscopies were employed. (3) Results: could survive normally after being fed on seven EPF species, including , , , , , , and . The first four fungi were the mite's favorites with their greater feeding amount and shorter developmental duration. Interestingly, the mite could also feed on and , but this led to the mite's death. After feeding on and , the mites began to die after 24 h, and the mortality rate reached 100% by 72 h. Observation under optical microscopy and scanning electron microscopy revealed that the conidia of and adhered to the mite's surface, but there was no evidence of penetration or invasion. However, dissection observation indicated that the two species germinate and grow within the mite's digestive tract, which implies that generalists with broad-spectrum hosts and the production of destruxins have acaricidal activity toward the mycophagous mites.
PubMed: 38930424
DOI: 10.3390/microorganisms12061042 -
Children (Basel, Switzerland) Jun 2024Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually...
Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually (SLIT). The aim of the current study was to evaluate and compare the efficacy of SCIT and SLIT for the treatment of allergic asthma in children. Our study included 69 children with allergic asthma who underwent immunotherapy for house dust mites or pollen for at least 3 consecutive years. After 3 years of SCIT and SLIT, the median number of asthma exacerbations in the last three months decreased from 2 to 0 ( < 0.01) and from 1 to 0 ( < 0.01), respectively. When comparing the efficacy of SCIT and SLIT, our study revealed a significantly better efficacy of SCIT only in terms of increasing lung function. The median increase in forced expiratory volume in one second (FEV1) after 3 years was 8% with SCIT and -1% with SLIT ( < 0.01). Daily controller therapy could be withdrawn or reduced in 9 out of 16 (56.3%) children who received it before SCIT ( < 0.01) and in 19 of 29 (65.6%) children who received it before SLIT ( < 0.01), but the difference in efficacy was not significant ( = 0.88). Both SCIT and SLIT are effective treatments for allergic asthma in children.
PubMed: 38929271
DOI: 10.3390/children11060692 -
Genes Jun 2024The grooming behavior of honeybees serves as a crucial auto-protective mechanism against mite infestations. Compared to , demonstrates more effective grooming behavior... (Comparative Study)
Comparative Study
The grooming behavior of honeybees serves as a crucial auto-protective mechanism against mite infestations. Compared to , demonstrates more effective grooming behavior in removing mites from the bodies of infested bees. However, the underlying mechanisms regulating grooming behavior remain elusive. In this study, we evaluated the efficacy of the auto-grooming behavior between and and employed RNA-sequencing technology to identify differentially expressed genes (DEGs) in bee brains with varying degrees of grooming behavior intensity. We observed that exhibited a higher frequency of mite removal between day 5 and day 15 compared to , with day-9 bees showing the highest frequency of mite removal in . RNA-sequencing results revealed the differential expression of the and genes in and the and genes in . Subsequent homology analysis identified the gene and gene of as homologous to the gene and gene of . These DEGs are annotated in the neuroactive ligand-receptor interaction pathway, the glutamatergic synaptic pathway, and the calcium signaling pathway. Moreover, , , , and may be closely related to the auto-grooming behavior of , conferring resistance against infestation. Our results further explain the relationship between honeybee grooming behavior and brain function at the molecular level and provide a reference basis for further studies of the mechanism of honeybee grooming behavior.
Topics: Animals; Bees; Varroidae; Grooming; Brain; Transcriptome; Mite Infestations; Gene Expression Profiling
PubMed: 38927699
DOI: 10.3390/genes15060763 -
Nature Communications Jun 2024Multi-host parasites pose greater health risks to wildlife, livestock, and humans than single-host parasites, yet our understanding of how ecological and biological...
Multi-host parasites pose greater health risks to wildlife, livestock, and humans than single-host parasites, yet our understanding of how ecological and biological factors influence a parasite's host range remains limited. Here, we assemble the largest and most complete dataset on permanently parasitic mammalian mites and build a predictive model assessing the probability of single-host parasites to become multi-hosts, while accounting for potentially unobserved host-parasite links and class imbalance. This model identifies statistically significant predictors related to parasites, hosts, climate, and habitat disturbance. The most important predictors include the parasite's contact level with the host immune system and two variables characterizing host phylogenetic similarity and spatial co-distribution. Our model reveals an overrepresentation of mites associated with Rodentia (rodents), Chiroptera (bats), and Carnivora in the multi-host risk group. This highlights both the potential vulnerability of these hosts to parasitic infestations and the risk of serving as reservoirs of parasites for new hosts. In addition, we find independent macroevolutionary evidence that supports our prediction of several single-host species of Notoedres, the bat skin parasites, to be in the multi-host risk group, demonstrating the forecasting potential of our model.
Topics: Animals; Host Specificity; Mites; Host-Parasite Interactions; Phylogeny; Mammals; Chiroptera; Ecosystem; Rodentia; Mite Infestations; Carnivora
PubMed: 38926409
DOI: 10.1038/s41467-024-49515-3 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma.
METHODS
In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (=49) and an SCIT group (=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT.
RESULTS
Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events.
CONCLUSIONS
SCIT is an effective and safe treatment for allergic asthma in children.
Topics: Humans; Asthma; Male; Child; Female; Animals; Prospective Studies; Injections, Subcutaneous; Pyroglyphidae; Child, Preschool; Desensitization, Immunologic; Adolescent
PubMed: 38926371
DOI: 10.7499/j.issn.1008-8830.2309137 -
Proceedings of the National Academy of... Jul 2024Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated...
Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926-970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation. To investigate the roles of the asthma-associated GATA3 enhancer region in experimental allergic airway inflammation, we first examined the correlation between GATA3 expression and the activation of the hG900 region was analyzed by flow cytometry and ChIP-qPCR. We found that The activation of enhancers in the hG900 region was strongly correlated to the levels of GATA3 in human peripheral T cell subsets. We next generated mice lacking the mG900 region (mG900KO mice) were generated by the CRISPR-Cas9 system, and the development and function of helper T cells and ILCs in mG900KO mice were analyzed in steady-state conditions and allergic airway inflammation induced by papain or house dust mite (HDM). The deletion of the mG900 did not affect the development of lymphocytes in steady-state conditions or allergic airway inflammation induced by papain. However, mG900KO mice exhibited reduced allergic inflammation and Th2 differentiation in the HDM-induced allergic airway inflammation. The analysis of the chromatin conformation around by circular chromosome conformation capture coupled to high-throughput sequencing (4C-seq) revealed that the mG900 region interacted with the transcription start site of with an influencing chromatin conformation in Th2 cells. These findings indicate that the mG900 region plays a pivotal role in Th2 differentiation and thus enhances allergic airway inflammation.
Topics: GATA3 Transcription Factor; Animals; Th2 Cells; Mice; Cell Differentiation; Asthma; Enhancer Elements, Genetic; Humans; Mice, Knockout; Inflammation; Hypersensitivity; Polymorphism, Single Nucleotide; Mice, Inbred C57BL
PubMed: 38923989
DOI: 10.1073/pnas.2320727121