Aspergillus Enhances Eosinophil and Neutrophil Extracellular DNA Trap Formation in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is characterized by inflammatory cell infiltration in the sinonasal mucosa. Eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) are prominently found in CRS. This study aimed to investigate the effect of airborne fungi, Alternaria alternata and Aspergillus fumigatus, on EET and NET formation. Nasal epithelial cells, eosinophils, and neutrophils were isolated from eosinophilic CRS (ECRS), non-ECRS (NECRS), and healthy control. We determined eosinophil and neutrophil transepithelial migration after fungal treatment. We then determined the release of EETs and NETs by fungi using Sytox Green staining and determined the role of reactive oxygen species (ROS) using ROS inhibitors. We identified more abundant EETs and NETs in ECRS than in NECRS. A. alternata and A. fumigatus enhanced eosinophil and neutrophil transepithelial migration. A. fumigatus strongly induced EET and NET formation in CRS and, simultaneously, suppressed fungal metabolic activity. EET formation in CRS is associated with nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and NET formation with NADPH-oxidase and mitochondrial ROS. A. fumigatus, but not A. alternata, induced EET and NET formation, and peripheral blood eosinophils and neutrophils exhibited different immune responses against A. fumigatus following the inflammatory status of the host. Aspergillus-fumigatus-induced EET and NET formation plays a crucial role in CRS pathogenesis.

Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.

Immunopathologic Role of Fungi in Chronic Rhinosinusitis.

Airborne fungi are ubiquitous in the environment and are commonly associated with airway inflammatory diseases. The innate immune defense system eliminates most inhaled fungi. However, some influence the development of chronic rhinosinusitis. Fungal CRS is thought of as not a common disease, and its incidence increases over time. Fungi are present in CRS patients and in healthy sinonasal mucosa. Although the immunological mechanisms have not been entirely explained, CRS patients may exhibit different immune responses than healthy people against airborne fungi. Fungi can induce Th1 and Th2 immune responses. In CRS, Th2-related immune responses against fungi are associated with pattern recognition receptors in nasal epithelial cells, the production of inflammatory cytokines and chemokines from nasal epithelial cells, and interaction with innate type 2 cells, lymphocytes, and inflammatory cells. Fungi also interact with neutrophils and eosinophils and induce neutrophil extracellular traps (NETs) and eosinophil extracellular traps (EETs). NETs and EETs are associated with antifungal properties and aggravation of chronic inflammation in CRS by releasing intracellular granule proteins. Fungal and bacterial biofilms are commonly found in CRS and may support chronic and recalcitrant CRS infection. The fungal-bacterial interaction in the sinonasal mucosa could affect the survival and virulence of fungi and bacteria and host immune responses. The interaction between the mycobiome and microbiome may also influence the host immune response, impacting local inflammation and chronicity. Although the exact immunopathologic role of fungi in the pathogenesis of CRS is not completely understood, they contribute to the development of sinonasal inflammatory responses in CRS.

Immunopathologic Role of Eosinophils in Eosinophilic Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a diverse chronic inflammatory disease of the sinonasal mucosa. CRS manifests itself in a variety of clinical and immunologic patterns. The histological hallmark of eosinophilic CRS (ECRS) is eosinophil infiltration. ECRS is associated with severe disease severity, increased comorbidity, and a higher recurrence rate, as well as thick mucus production. Eosinophils play an important role in these ECRS clinical characteristics. Eosinophils are multipotential effector cells that contribute to host defense against nonphagocytable pathogens, as well as allergic and nonallergic inflammatory diseases. Eosinophils interact with Staphylococcus aureus, Staphylococcal enterotoxin B, and fungi, all of which were found in the tissue of CRS patients. These interactions activate Th2 immune responses in the sinonasal mucosa and exacerbate local inflammation. Activated eosinophils were discovered not only in the tissue but also in the sinonasal cavity secretion. Eosinophil extracellular traps (EETs) are extracellular microbes trapping and killing structures found in the secretions of CRS patients with intact granule protein and filamentous chromatic structures. At the same time, EET has a negative effect by causing an epithelial barrier defect. Eosinophils also influence the local tissue microenvironment by exchanging signals with other immune cells and structural cells. As a result, eosinophils are multifaceted leukocytes that contribute to various physiologic and pathologic processes of the upper respiratory mucosal immune system. The goal of this review is to summarize recent research on the immunopathologic properties and immunologic role of eosinophils in CRS.

Fibrous dysplasia of the maxillary bone secondary to sinus surgery in an elderly patient: A case report.

Fibrous dysplasia (FD) is a rare benign disease that replaces a normal bone with abnormal fibrous and weak osseous tissue. It is usually detected in childhood and rarely occurs in old age. Although the disease is known to be caused by a genetic mutation, only a single case of FD secondary to surgery is reported in the literature. We report a case of monostotic FD of the maxillary sinus in a 70-year-old Asian woman who presented with incidental calcific lesion in the maxillary sinus on a brain computed tomography scan. At 32 months prior to presentation, the patient had undergone an endoscopic sinus surgery for a fungal ball of the same sinus. The lesion was removed by endoscopic surgery, and the histopathological evidence was consistent with FD. To the best of our knowledge, this is the second case of a postsurgical craniofacial FD, and a rare case that occurred in old age.