Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders

Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology

Innate lymphocyte cells in asthma phenotypes

T helper type 2 (TH2) cells were previously thought to be the main initiating effector cell type in asthma; however, exaggerated TH2 cell activities alone were insufficient to explain all aspects of asthma. Asthma is a heterogeneous syndrome comprising different phenotypes that are characterized by their different clinical features, treatment responses, and inflammation patterns. The most-studied subgroups of asthma include TH2-associated early-onset allergic asthma, late-onset persistent eosinophilic asthma, virus-induced asthma, obesity-related asthma, and neutrophilic asthma. The recent discovery of human innate lymphoid cells capable of rapidly producing large amounts of cytokines upon activation and the mouse data pointing to an essential role for these cells in asthma models have emphasized the important role of the innate immune system in asthma and have provided a new means of better understanding asthma mechanisms and differentiating its phenotypes

Children’s residential exposure to selected allergens and microbial indicators: endotoxins and (1→3)-β-D-glucans

Objectives: The study was aimed at assessment of exposure to endotoxins, (1→3)-β-D-glucans and mite, cockroach, cat, dog allergens present in settled dust in premises of children as agents which may be significantly correlated with the occurrence of allergic symptoms and diseases in children. Materials and Methods: The study covered 50 homes of one- or two-year-old children in Poland. Samples of settled dust were taken from the floor and the child's bed. The levels of (1→3)-β-D-glucans (floor), endotoxins (floor) and allergens of mite, cat, dog and cockroach (floor and bed) were analyzed. Results: Average geometric concentrations (geometric standard deviation) of endotoxins, (1→3)-β-D-glucans, Der p1, Fel d1, Can f1 and Bla g1 in children homes were on the floor 42 166.0 EU/g (3.2), 20 478.4 ng/g (2.38), 93.9 ng/g (6.58), 119.8 ng/g (13.0), 288.9 ng/g (3.4), 0.72 U/g (4.4) and in their beds (only allergens) 597.8 ng/g (14.2), 54.1 ng/g (4.4), 158.6 ng/g (3.1) 0.6 U/g (2.9), respectively. When the floor was covered with the carpet, higher concentrations of endotoxins, (1→3)-β-D-glucans and allergens (each type) were found in the settled dust (p < 0.05). The trend was opposite in case of allergens (except dog) analyzed from bed dust and significantly higher concentrations were found in the rooms with smooth floor (p < 0.05). Conclusions: Among the analyzed factors only the type of floor significantly modified both the level of biological indicators and allergens. The results of this study could be the base for verifying a hypothesis that carpeting may have a protective role against high levels of cockroach, dog and cat allergens

Group 2 Innate Lymphoid Cell Proportions Are Diminished in Young Helminth Infected Children and Restored by Curative Anti-helminthic Treatment

BACKGROUND:Group 2 Innate lymphoid cells (ILC2s) are innate cells that produce the TH2 cytokines IL-5 and IL-13. The importance of these cells has recently been demonstrated in experimental models of parasitic diseases but there is a paucity of data on ILC2s in the context of human parasitic infections and in particular of the blood dwelling parasite Schistosoma haematobium. METHODOLOGY/PRINCIPAL FINDINGS:In this case-control study human peripheral blood ILC2s were analysed in relation to infection with the helminth parasite Schistosoma haematobium. Peripheral blood mononuclear cells of 36 S. haematobium infected and 36 age and sex matched uninfected children were analysed for frequencies of ILC2s identified as Lin-CD45+CD127+CD294+CD161+. ILC2s were significantly lower particularly in infected children aged 6-9 years compared to healthy participants. Curative anti-helminthic treatment resulted in an increase in levels of the activating factor TSLP and restoration of ILC2 levels. CONCLUSION:This study demonstrates that ILC2s are diminished in young helminth infected children and restored by removal of the parasites by treatment, indicating a previously undescribed association between a human parasitic infection and ILC2s and suggesting a role of ILC2s before the establishment of protective acquired immunity in human schistosomiasis

Marqueurs de sévérité et marqueurs prédictifs de réponse au traitement dans l’asthme sévère

International audienceAsthma is a multifactorial disease with complex pathophysiology. Knowledge of its immunopathology and inflammatory mechanisms is progressing and has led to the development over recent years of increasingly targeted therapeutic strategies. The objective of this review is to pinpoint the different predictive markers of asthma severity and therapeutic response. Obesity, nasal polyposis, gastroesophageal reflux disease and intolerance to aspirin have all been considered as clinical markers associated with asthma severity, as have functional markers such as bronchial obstruction, low FEV1, small daily variations in FEV1, and high FeNO. While sinonasal polyposis and allergic comorbidities are associated with better response to omalizumab, nasal polyposis or long-term systemic steroid use are associated with better response to antibodies targeting the IL5 pathway. Elevated total IgE concentrations and eosinophil counts are classic biological markers regularly found in severe asthma. Blood eosinophils are predictive biomarkers of response to anti-IgE, anti-IL5, anti-IL5R and anti-IL4R biotherapies. Dupilumab is particularly effective in a subgroup of patients with marked type 2 inflammation (long-term systemic corticosteroid therapy, eosinophilia≥150/μl or FENO>20 ppb). Chest imaging may help to identify severe patients by seeking out bronchial wall thickening and bronchial dilation. Study of the patient's environment is crucial insofar as exposure to tobacco, dust mites and molds, as well as outdoor and indoor air pollutants (cleaning products), can trigger asthma exacerbation. Wider and more systematic use of markers of severity or response to treatment could foster increasingly targeted and tailored approaches to severe asthma.L’asthme est une maladie multifactorielle dont la physiopathologie est complexe. Les connaissances de l’immunopathologie et des mécanismes inflammatoires ont progressé permettant ces dernières années, le développement de stratégies thérapeutiques de plus en plus ciblées.L’objectif de cette revue est de décrire les différents marqueurs prédictifs de la sévérité de l’asthme et de la réponse thérapeutique. Sur le plan clinique, l’obésité, la polypose nasale, le reflux gastro-œsophagien, l’intolérance à l’aspirine ont été décrits comme des marqueurs associés à la sévérité de l’asthme.Des marqueurs fonctionnels tels qu’une obstruction bronchique, un VEMS bas, de faibles variations journalières de VEMS et une FeNO élevé ont également été décrits comme associés à la sévérité de l’asthme. La polypose naso-sinusienne et les comorbidités allergiques sont associées à une meilleure réponse à l’omalizumab alors que la polypose nasale ou l’utilisation d’une corticothérapie systémique au long cours est associée à une meilleure réponse aux anticorps dirigés contre la voie de l’IL5. Des concentrations d’IgE totales et un taux d’éosinophiles élevés sont des marqueurs biologiques classiquement retrouvés dans l’asthme sévère. L’éosinophilie sanguine est un biomarqueur permettant de prédire la réponse aux biothérapies anti-IgE, anti-IL5, anti-IL5R et anti-IL4R. Le dupilumab s’est révélé efficace en particulier dans le sous-groupe de patients présentant une inflammation de type 2 marquée (corticothérapie systémique au long cours, éosinophilie≥150/μl ou FENO>20 ppb). L’imagerie thoracique pourrait également contribuer à identifier des patients sévères par la recherche d’un épaississement de la paroi bronchique et une dilatation des bronches. L’étude de l’environnement est cruciale puisque des allergènes et des polluants aggravent la maladie asthmatique.Une utilisation plus large et systématique des marqueurs de sévérité ou de réponse au traitement pourrait permettre une approche de plus en plus précise et personnalisée

Indoor dust and air concentrations of endotoxin in urban and rural environments.

Rural dairy farming is associated with high exposure to indoor endotoxins as compared to rural nonfarming houses and urban houses. The time spent on the mattress (7 h for an adult) and of the proximity of the contaminated source should be taken into account with the other causes of exposure. Studies in European children from a farming background have shown that these children have a reduced risk of asthma and atopic sensitization compared to their urban counterparts. It has been suggested that this might be due to exposure to high levels of endotoxin in the farming environment. The aim of this study was to compare indoor endotoxin concentrations in air and dust samples from randomly selected urban and rural dwellings. In the rural area, endotoxins were analysed in farmhouses and nonfarmhouses as well as housing characteristics, lifestyle factors and agricultural practices likely to influence air and dust endotoxin levels. Endotoxin levels were significantly higher in floor (6600 ± 6100 vs 3600 ± 5600 and 3800 ± 17,000 ng g⁻¹; P < 0·001) and mattress dust (2900 ± 4100 vs 1100 ± 2400 and 800 ± 2600 ng g⁻¹; P < 0·001) from farmhouses compared to other rural and urban homes. However, no difference was observed between endotoxin concentrations in the air of urban and rural houses, and airborne endotoxin levels did not correlate to dust levels. Lack of ventilation and direct entry into the house were correlated with an increase in dust endotoxin levels. These results confirm that dairy farming is associated with high exposure to endotoxins in indoor dust samples. No difference was observed between indoor airborne concentrations between urban and rural houses. These results suggest that measuring endotoxin in dust is the most relevant method to assess endotoxin exposure