Search Results (51)

Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after a SARS-CoV-2 infection are missing. Therefore, in this study, we performed blood eosinophil, neutrophil, and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after the hospitalization of patients with severe SARS-CoV-2 infections. Blood cell counts were reported at seven different timepoints over the 30-day period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate a 95% drop in the blood eosinophil count by D1, with eosinophils displaying a phenotype defined as CD69/CD63/CD125^high and CCR3/CD44^low during the early phases of hospitalization. Conversely, by D7 the neutrophil count increased significantly and displayed an immature, activated, and immunosuppressive phenotype (i.e., 3% of CD10/CD16^low and CD10^lowCD177^high, 6.7% of CD11b^highCD62L^low, and 1.6% of CD16^highCD62L^low), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64^high and CD32^low monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with a likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils and the functions of the eosinophils and the monocytes, as well as these innate immune cell types, interplays need to be further investigated. Full article

Background: The pathophysiology of non-IgE-mediated cow’s milk allergy is mostly unknown. Previous studies suggested a mechanism mediated by T cells, but this was not confirmed in subsequent studies. The aim of this study was to investigate the immunological mechanisms, especially the role of regulatory T cells (Tregs), in the pathophysiology of allergic proctocolitis (FPIAP). Methods: A prospective observational study was conducted on infants with FPIAP and a control group of healthy infants with similar ages. The main variables were lymphocyte populations, included Tregs, which were extracted from peripheral blood and processed immediately by flow cytometry at two time points: in the acute phase (“T0”) and after clinical resolution (“Tres”). Results: A total of 32 patients with FPIAP and 10 healthy infants were enrolled. There was a higher T-CD4 memory cell count, increased numbers of regulatory B cells and a higher percentage of Tregs (p < 0.01) in patients with acute FPIAP in contrast to the healthy group. The levels of granulocytes (mainly eosinophils), dendritic cells (mDC2) and NK16+56- cells were also significantly higher in the FPIAP group. NK16+56- cells and the number of granulocytes appeared to be the best markers for distinguishing between the healthy and FPIAP infants based on the ROC curves. Conclusions: FPIAP does not appear to have an immune mechanism mediated by T cells, but it may be associated with innate immunity responses characterized by an increase in NK16+56- cells, eosinophils and dendritic cells. These cells could be evaluated in future studies as possible markers of non-IgE-mediated cow’s milk protein allergy. Full article

As aquaculture expands, plant-based feeds are increasingly used, but some fish species poorly tolerate them, affecting health and growth. Probiotics can help counter these effects by improving digestion, nutrient absorption, and immunity. This study evaluated the effect of dietary incorporation of Bacillus subtilis FI99 on the intestinal health of meagre. A nutritional challenge was performed with a practical control diet and three diets higher in plant-based ingredients: one without probiotic and two with probiotic incorporated at 1 × 10⁹ CFU g⁻¹ and 5.5 × 10¹¹ CFU g⁻¹. Histomorphological analysis was used to assess intestinal health and validate previously established machine learning models in predicting fish nutritional status. No differences were observed in zootechnical performance and biometric indexes. Most effects were observed in the anterior intestinal section, where probiotics improved total area, lumen area, lumen maximum diameter, total maximum diameter, villi area, and villi + lumen area. Additionally, probiotics improved supranuclear vacuole size, eosinophilic granulocytes, and intraepithelial leukocytes presence in anterior and intermediate sections. Machine learning models could not accurately predict the nutritional status of fish. Overall, the study indicates that dietary inclusion of B. subtilis enhances the intestinal health of meagre fed plant-based diets. Machine learning models require further development for improved accuracy. Full article

Eosinophils are granulocytes involved in the effector phase of type 2 T cell immune responses, which are elevated in inflammatory conditions like ulcerative colitis (UC) and other allergic diseases. UC is a chronic inflammatory colon disease, marked by excessive eosinophil infiltration and elevated Th2 cytokines, which contribute to mucosal inflammation and tissue damage. Dietary factors, including certain organic acids, can influence UC progression by modulating gut immune responses. This research is the first to explore the dose-dependent effects of tartaric acid (TA), a naturally occurring organic acid widely used in the food industry, on eosinophil activation and Th2 cytokine response in both normal mice and a dextran sulfate sodium (DSS)-induced colitis model. Normal mice were treated with TA at varying doses (5 µg, 25 µg, and 50 µg/mouse/day), while colitis mice received 50 µg TA. Eosinophil activation markers (CD11b+, SiglecF+, and CCR3+), Th2 cytokines (IL-4, IL-13, and IL-31), and IL-17 were assessed in peripheral blood leukocytes, lymph nodes, and splenocytes using flow cytometry. Additionally, mRNA expression levels of eosinophil-associated chemokines and cytokines in the splenocytes were quantified with real-time qPCR. Our results demonstrate a dose-dependent effect of TA, with the highest dose (50 µg) significantly increasing eosinophil activation markers, Th2 cytokines, IL-17, and mRNA expression of SiglecF, CCL11, and toll-like receptor 4 in normal mice. In colitis mice, treatment with 50 µg TA showed marked increases in IL-13 levels compared to those of untreated colitis mice, reflecting increased eosinophil recruitment to inflamed tissues. Moreover, mRNA expression of IL-5Rα was elevated in normal mice and colitis mice administered with TA. These results suggest that TA enhances eosinophil proliferation, the upregulation of their regulatory molecules, and Th2 immune profiles, potentially worsening the severity of colitis. Full article

Myeloproliferative neoplasm (MPN) with eosinophilia associated with FIP1L1-PDGFRA is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent FIP1L1-PDGFRA T674I and PTPN11 (p.E76D) mutations in a 38-year-old male patient with MPN and eosinophilia. The patient initially responded to imatinib but developed resistance after ten months, leading to severe spinal cord compression caused by granulocytic sarcoma. Despite undergoing radiotherapy, chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), the disease progressed. Although full donor chimerism was achieved post-transplant, the patient relapsed shortly afterward with eosinophilia, splenomegaly, and constitutional symptoms. Further treatments, including sorafenib and decitabine, failed to control the disease, and the patient ultimately died from multiorgan failure. This case illustrates the therapeutic challenges associated with FIP1L1-PDGFRA T674I-positive eosinophilic disorder, especially when compounded by the PTPN11 mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease. Full article

Background/Objectives: Although a “forgotten” disease in developed countries, typhoid fever remains a significant global health problem, especially in regions with inadequate sanitation and overcrowding. Despite medical advances, this systemic bacterial infection, caused by Salmonella Typhi, continues to affect millions worldwide. Accurate diagnosis and timely treatment are crucial to prevent severe complications and mortality. Even though antibiotic therapy is effective, the emergence of drug-resistant strains is a growing challenge. Methods: We present a series of cases encountered in a tertiary infectious disease hospital in Romania over 15 years. Results: The hospitalised patients were mainly from Sub-Saharan Africa and the Indian subcontinent; the median time between the onset of the first symptoms and hospital admission was 15 days. The symptoms encountered along with fever were headache, chills, cough, diarrhoea and tachycardia, an unusual feature in the clinical picture of this disease. Aneosinophilia (the absence of peripheral eosinophilic granulocytes) was the most frequently encountered laboratory finding, followed by increased serum transaminases and inflammatory syndrome. Conclusions: S. Typhi was generally identified from blood culture, demonstrating, except in one case, resistance to ciprofloxacin and, in several cases, multi-drug resistance (MDR). In this series of cases, all strains were sensitive to ceftriaxone. Full article

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms “eosinophilic pneumonia AND antidepressants”. Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis. Full article

Feline Panleukopenia (FPL) infection is caused by feline panleukopenia virus (FPV), and it is considered one of the most severe cat’s infectious diseases. Since there is no specific antiviral treatment for FPL, the therapeutic protocol usually is focused on fluid therapy and supportive care. However, filgrastim, a granulocyte colony-stimulating factor (G-CSF) used in human medicine to treat neutropenia and leukopenia, has been lately used in treating FPV disease, providing promising results. During January 2022 and September 2024, twenty-two cats diagnosed with feline panleukopenia virus were subjected to filgrastim (Zarzio^®, Sandoz, Kundl, Austria) administration at a dose of 6 µg/kg for 3 consecutive days. The 4th day was a break day, and in the 5th day, the complete blood count was repeated. White blood cells, lymphocytes, monocytes, neutrophils and eosinophils parameters improved after Zarzio^® administration, with a significant statistical difference (p < 0.01) when their values between day 1 (pre Zarzio^® administration) and day 5 (post Zarzio^® administration) were analysed. However, red blood cells, haemoglobin, haematocrit and platelets parameters registered a considerable reduction from day 1 to day 5 with a significant statistical difference (p < 0.01), considered as post-administration side effects. In our study, the survival rate following Zarzio^® administration was 100%, suggesting that the protocol involving three doses is effective in restoring the leukopenia and neutropenia. Full article

Psychosocial stress has been proposed to induce a redistribution of immune cells, but a comparison with an active placebo-psychosocial stress control condition is lacking so far. We investigated immune cell redistribution due to psychosocial stress compared to that resulting from an active placebo-psychosocial stress but otherwise identical control condition. Moreover, we tested for mediating effects of endocrine parameters and blood volume changes. The final study sample comprised 64 healthy young men who underwent either a psychosocial stress condition (Trier Social Stress Test; TSST; n = 38) or an active placebo-psychosocial stress control condition (PlacTSST; n = 26). Immune cell counts and hemoglobin, epinephrine, norepinephrine, ACTH, renin, and aldosterone levels, as well as those of saliva cortisol, were determined before and up to 30 min after the TSST/PlacTSST. The TSST induced greater increases in total leukocyte, monocyte, and lymphocyte levels as compared to the PlacTSST (p’s ≤ 0.001), but in not granulocyte counts. Neutrophil granulocyte counts increased in reaction to both the TSST and PlacTSST (p’s ≤ 0.001), while eosinophil and basophil granulocyte counts did not. The psychosocial stress-induced increases in immune cell counts from baseline to peak (i.e., +1 min after TSST cessation) were independently mediated by parallel increases in epinephrine (ab’s ≤ −0.43; 95% CIs [LLs ≤ −0.66; ULs ≤ −0.09]). Subsequent decreases in immune cell counts from +1 min to +10 min after psychosocial stress cessation were mediated by parallel epinephrine, renin, and blood volume decreases (ab’s ≥ 0.17; 95% CIs [LLs ≥ 0.02; ULs ≥ 0.35]). Our findings indicate that psychosocial stress specifically induces immune cell count increases in most leukocyte subpopulations that are not secondary to the physical or cognitive demands of the stress task. Increases in the number of circulating neutrophil granulocytes, however, are not psychosocial stress-specific and even occur in situations with a low probability of threat or harm. Our findings point to a major role of epinephrine in mediating stress-induced immune cell count increases and of epinephrine, renin, and blood volume changes in mediating subsequent immune cell count decreases from +1 min to +10 min after psychosocial stress cessation. Full article

The Sysmex XN-1000V provides a percentage and concentration of basophils from the WNR scattergram, as for human samples, but this method has been shown to be irrelevant in cats. This study aimed to characterize the feline basophil distribution on the WDF channel and to preliminarily evaluate the performance of a new basophil gate on the WDF channel. Cases of feline basophilia were retrospectively retrieved and the scattergram from the WDF and WNR channels were evaluated for any consistent pattern. A new gating setting for the WDF channel was created to include the suspected basophil region. This new gating was applied retrospectively to identified basophilia cases and prospectively to randomly selected feline cases. Manual, WNR, and new WDF methods for basophil identification were compared. Nine cases of feline basophilia were identified. A characteristic WDF scattergram was identified in seven of the nine cases. A new gate was created on the WDF channel and applied to these and 34 additional cases. The comparison study showed that the new method of basophil quantification using the WDF scattergram correlated better with the manual method than the Sysmex XN-1000V method using the WNR scattergram. Basophil concentration in feline peripheral blood can be determined using a new gate on the WDF channel of the Sysmex XN-1000V, which provides better performance than the WNR channel and is comparable to the manual method. Full article

Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding RNAs (lncRNAs) are known to be involved in eosinophilic conditions, their specific expression and functions within eosinophils have not been thoroughly investigated, largely due to the reliance on tissue homogenates. In an effort to address this gap, we analyzed publicly available high-throughput RNA sequencing data to identify lncRNAs associated with eosinophilic conditions. Among the identified lncRNAs, ITGB2 antisense RNA 1 (ITGB2-AS1) was significantly downregulated in blood eosinophils from patients with hypereosinophilia. To further explore its role in eosinophil biology, we generated a stable ITGB2-AS1 knockdown in the HL-60 cell line. Interestingly, ITGB2-AS1 deficiency led to impaired eosinophil differentiation, as evidenced by a reduction in cytoplasmic granules and decreased expression of key eosinophil granule proteins, including eosinophil peroxidase (EPX) and major basic protein-1 (MBP-1). Additionally, ITGB2-AS1-deficient cells exhibited compromised eosinophil effector functions, with reduced degranulation and impaired production of reactive oxygen species (ROS). These findings suggest that ITGB2-AS1 plays a pivotal role in eosinophil differentiation and function, positioning it as a novel regulator in eosinophil biology. Full article

Several studies have described the proteomic profile of different immune cell types, but only a few have also analysed the content of their delivered small extracellular vesicles (sEVs). The aim of the present study was to compare the protein signature of sEVs delivered from granulocytes (i.e., neutrophils and eosinophils) and CD4⁺ T cells (i.e., TH1, TH2, and TH17) to identify potential biomarkers of the inflammatory profile in chronic inflammatory diseases. Qualitative (DDA) and quantitative (DIA-SWATH) analyses of in vitro-produced sEVs revealed proteome variations depending on the cell source. The main differences were found between granulocyte- and TH cell-derived sEVs, with a higher abundance of antimicrobial proteins (e.g., LCN2, LTF, MPO) in granulocyte-derived sEVs and an enrichment of ribosomal proteins (RPL and RPS proteins) in TH-derived sEVs. Additionally, we found differentially abundant proteins between neutrophil and eosinophil sEVs (e.g., ILF2, LTF, LCN2) and between sEVs from different TH subsets (e.g., ISG15, ITGA4, ITGB2, or NAMPT). A “proof-of-concept” assay was also performed, with TH2 biomarkers ITGA4 and ITGB2 displaying a differential abundance in sEVs from T2^high and T2^low asthma patients. Thus, our findings highlight the potential use of these sEVs as a source of biomarkers for diseases where the different immune cell subsets studied participate, particularly chronic inflammatory pathologies such as asthma or chronic obstructive pulmonary disease (COPD). Full article

The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body’s defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research. Full article

Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients’ sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management. Full article

The chronic inflammatory component of asthma is propagated by granulocytes, including neutrophils and eosinophils, in the peripheral circulation and airway. Previous studies have suggested that these cells have an altered expression of adhesion-related molecules and a propensity for the release of granule contents that may contribute to tissue damage and enhance inflammatory complications in patients with status asthmaticus. The goal of this prospective cohort study at a tertiary care pediatric hospital with a large population of asthma patients was to assess the role of granulocyte-based inflammation in the development of asthma exacerbation. Subjects were enrolled from two patient populations: those with mild-to-moderate asthma exacerbations seen in the emergency department and those with severe asthma admitted to the intensive care unit (PICU). Clinical data were collected, and blood was drawn. Granulocytes were immediately purified, and the phenotype was assessed, including the expression of cell surface markers, elastase release, and cytokine production. Severe asthmatics admitted to the PICU displayed a significantly higher total neutrophil count when compared with healthy donors. Moreover, little to no eosinophils were found in granulocyte preparations from severe asthmatics. Circulating neutrophils from severe asthmatics admitted to the PICU displayed significantly increased elastase release ex vivo when compared with the PMN from healthy donors. These data suggest that the neutrophil-based activation and release of inflammatory products displayed by severe asthmatics may contribute to the propagation of asthma exacerbations. Full article