Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions

In order to investigate the relationship between airways inflammation and disease severity, and improve the understanding of persistent asthma, 74 asthmatics, with disease severity ranging from intermittent, to mild to moderate and severe persistent (classified according to the Global Initiative for Asthma [GINA] guidelines), and 22 nonatopic control subjects were studied using the method of induced sputum. Sputum was analyzed for total and differential cell counts concentrations of albumin, and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase, inflammatory mediators reflecting eosinophil, neutrophil, and mast cell activation. Asthma severity (assessed by FEV(1), peak expiratory flow [PEF] variability, and daily symptom scores) and methacholine airways responsiveness were related to sputum eosinophilia and ECP. In addition, sputum neutrophilia and MPO levels correlated, albeit weakly, with PEF variability and symptom scores, respectively. Tryptase concentrations were raised in mild to moderate asthmatics. Albumin concentrations were significantly raised across the spectrum of asthma severity and correlated with those of tryptase and ECP. Despite treatment with either high doses of inhaled corticosteroids or oral corticosteroids, prominent eosinophilic inflammation with raised ECP was noted. This study points to persistent, disease severity-related airways inflammation in asthma, involving eosinophils, mast cells, and neutrophils, which is evident despite treatment with corticosteroids.

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals.

BackgroundPhenotyping asthma according to airway inflammation allows identification of responders to targeted therapy. Induced sputum is technically demanding. We aimed to identify predictors of sputum inflammatory phenotypes according to easily available clinical characteristics.MethodsThis retrospective study was conducted in 508 asthmatics with successful sputum induction recruited from the University Asthma Clinic of Liege. Receiver-operating characteristic (ROC) curve and multiple logistic regression analysis were used to assess the relationship between sputum eosinophil or neutrophil count and a set of covariates. Equations predicting sputum eosinophils and neutrophils were then validated in an independent group of asthmatics.ResultsEosinophilic (≥3%) and neutrophilic (≥76%) airway inflammation were observed in 46% and 18% of patients respectively. Predictors of sputum eosinophilia ≥3% were high blood eosinophils, FENO and IgE level and low FEV1/FVC. The derived equation was validated with a Cohen’s kappa coefficient of 0.59 (p < 0.0001). ROC curves showed a cut-off value of 220/mm3 (AUC = 0.79, p < 0.0001) or 3% (AUC = 0.81, p < 0.0001) for blood eosinophils to identify sputum eosinophilia ≥3%. Independent predictors of sputum neutrophilia were advanced age and high FRC but not blood neutrophil count.ConclusionEosinophilic and paucigranulocytic asthma are the dominant inflammatory phenotypes. Blood eosinophils provide a practical alternative to predict sputum eosinophilia but sputum neutrophil count is poorly related to blood neutrophils.