Introduction
Eosinophils, the second least represented granulocyte subpopulation in circulating blood, are gaining significant attention in the scientific community due to their complex role in a wide spectrum of localized and widespread inflammatory conditions, malignancies, and blood clotting disorders. These white blood cells are crucial for controlling parasitic infections and are also involved in protective functions in combating bacterial and viral infectious agents, such as the human immunodeficiency virus (HIV). However, the potential toxicity of eosinophil-released compounds to host tissues and the dysregulation of hemostasis pose challenges to their role in the immune response.
What Is the Development and Homeostasis of Eosinophils?
Eosinophils are derived from hematopoietic stem cells residing in the bone marrow., going through a complex maturation and differentiation process influenced by specific cytokines like interleukin-five (IL-5), interleukin-three (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as the transcription factor GATA-one. In healthy individuals, eosinophils circulate at low levels in the blood, with their production, trafficking, and apoptosis tightly regulated to maintain homeostasis. An imbalance in this equilibrium can precipitate the onset of various health conditions, like eosinophilia or eosinopenia.
What Are the Immune Functions of Eosinophils?
Eosinophils are vital in the immune response against parasitic infections, particularly helminth infestations. Their cytoplasmic granules contain cytotoxic proteins like major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase (EPO), which are effective against various parasites. Additionally, eosinophils release reactive oxygen species (ROS) and secrete cytokines, contributing to other immune cells' inflammatory response and recruitment.
How Do Eosinophils Contribute to Allergy and Asthma?
Eosinophils are key players in the pathogenesis of allergic diseases like asthma, eczema, and allergic rhinitis. Allergen exposure triggers the release of cytokines like IL-five, which promote eosinophil recruitment to the affected tissues. Once activated, eosinophils release their cytotoxic granule proteins and mediators, leading to airway inflammation, tissue damage, and the bronchial hyperresponsiveness characteristic of asthma.
What Is the Role of Eosinophils in Gastrointestinal Disorders?
Eosinophils play a crucial role in the development of various gastrointestinal disorders, including eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EGE), and inflammatory bowel diseases (IBD). In EoE and EGE, eosinophil accumulation and activation in the esophagus or gastrointestinal tract lead to tissue injury and symptom manifestation. In IBD, eosinophils contribute to the inflammatory process, and their levels correlate with disease activity.
How Do Eosinophils Influence Tumor Immunity?
Emerging evidence suggests that eosinophils have a complex role in tumor immunity, with both pro-tumorigenic and anti-tumorigenic effects reported. Eosinophils can promote tumor rejection through cytotoxic mechanisms, antibody-dependent cell-mediated cytotoxicity (ADCC), and modulation of the tumor microenvironment. However, in certain cancer types, eosinophils may contribute to tumor progression by promoting angiogenesis, suppressing anti-tumor immunity, and facilitating metastasis.
What Is the Role of Eosinophils in Tissue Repair and Remodeling?
Beyond their immune functions, eosinophils participate in tissue repair and remodeling processes. Their secretion of cytokines and growth factors like transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) can influence fibroblast proliferation, extracellular matrix deposition, and angiogenesis. However, excessive or persistent eosinophil activation can also contribute to tissue damage and fibrosis in conditions like asthma and eosinophilic disorders.
Eosinophils also play a role in regulating the immune response and promoting the resolution of inflammation. They can produce anti-inflammatory mediators like lipoxins and resolvins, which help to dampen the inflammatory response and facilitate tissue repair. Additionally, eosinophils can induce the production of regulatory T cells, which suppress excessive immune responses and maintain immune homeostasis.
What Are Eosinophilic Disorders?
Eosinophilic disorders are a group of conditions characterized by an abnormal accumulation of eosinophils in various tissues, leading to organ damage and dysfunction. These disorders can be classified as primary (e.g., hypereosinophilic syndromes) or secondary (e.g., associated with allergic, infectious, or neoplastic conditions). Primary eosinophilic disorders are often caused by genetic mutations or clonal eosinophil proliferation, while secondary eosinophilic disorders result from an underlying condition that triggers eosinophil activation and recruitment. Common manifestations of eosinophilic disorders include organ involvement (e.g., lungs, heart, skin, and gastrointestinal tract), which can lead to various complications. Prompt diagnosis and management of eosinophilic disorders are crucial to preventing potentially life-threatening complications like heart failure, respiratory failure, or gastrointestinal complications.
How Are Eosinophils Therapeutically Targeted?
Given the pivotal role of eosinophils in various inflammatory and hypereosinophilic disorders, therapeutic strategies targeting eosinophils have gained significant attention. Monoclonal antibodies like mepolizumab and benralizumab, which target IL-five or its receptor, have proven effective in reducing eosinophil levels and improving clinical outcomes in severe eosinophilic asthma. Other approaches are also being explored, like targeting eosinophil-specific surface molecules or inhibiting eosinophil recruitment and activation. Small molecule inhibitors targeting eosinophil-related signaling pathways or cytokine receptors are under investigation.
What Is the Difference Between Eosinophilia and Eosinopenia?
Eosinophilia and eosinopenia are two opposite conditions related to the count of eosinophils, a specific variety of leukocytes (white blood cells) found in the bloodstream. Eosinophils are crucial components of the immune system, playing roles in defending the body against pathogens, including parasites and allergens. The differences between eosinophilia and eosinopenia lie in the levels of eosinophils present in the blood.
Eosinophilia is a condition where the number of eosinophils in the blood is higher than normal. This condition is characterized by an increased count of eosinophils, which can be indicative of various health conditions, including allergic diseases, parasitic infections, and certain autoimmune disorders. High levels of eosinophils are associated with the body's response to foreign invaders, such as parasites, allergens, and infections, where eosinophils are involved in the immune response.
Eosinopenia is the opposite phenomenon, where the number of eosinophils in the blood is lower than normal. This condition is marked by a decreased count of eosinophils, which can be seen in various situations, including certain immune deficiencies, bone marrow disorders, and certain chronic illnesses. Eosinopenia can make the body more susceptible to infections and allergic reactions, as the eosinophils assume a vital function in the body's immune response to combat parasites and allergens.
The diagnosis of eosinopenia can be challenging due to the low number of eosinophils in the blood and the fluctuations in eosinophil levels throughout the day. The definition of eosinopenia varies in clinical practice, with one common definition being an absolute eosinophil count of less than 50 cells/μLiter of blood. Other definitions include less than 10 cells/μLiter, while some clinical laboratories classify 0 cells/μLiter as within the acceptable range.
Both eosinophilia and eosinopenia can have significant health implications, affecting the body's ability to fight off infections and respond to allergens.
What Are the Future Perspectives in Eosinophil Research?
Despite the substantial progress in understanding eosinophil biology and its roles in health and disease, several areas warrant further investigation. Unraveling the complex interactions between eosinophils and other immune cells and their tissue-specific functions could provide valuable insights into their homeostatic and pathogenic mechanisms.
Conclusion
Eosinophils have emerged as versatile and multifunctional cells, playing diverse roles in immune response, tissue repair, and disease pathogenesis. Their contributions to allergic diseases, gastrointestinal disorders, tumor immunity, and eosinophilic disorders have been well-established. However, the intricate balance between their protective and pathogenic functions intrigues researchers. Further exploration of eosinophil biology and therapeutic targeting holds promise for improving the management of eosinophil-related disorders and our understanding of these remarkable cells.
