Eosinophils are white blood cells that serve a function in the immune system. These cells are defined by large, highly visible internal structures called granules. While the primary function of eosinophils is to protect the host from specific biological threats, their overactivity drives several chronic inflammatory diseases. Understanding the dual nature of these cells—as both defenders and potential sources of tissue damage—is fundamental.
Basic Structure and Origin
Eosinophils belong to granulocytes, defined by prominent granules. Their nucleus typically possesses two lobes connected by a thin strand, giving it a spectacle-like shape. The cell’s namesake comes from its strong affinity for the acidic stain eosin, which causes the granules to appear a brilliant red or pink under a microscope.
These cells originate in the bone marrow from hematopoietic stem cells. Their development is heavily influenced by specific signaling proteins, most notably Interleukin-5 (IL-5). Once mature, eosinophils circulate in the bloodstream before migrating into various tissues.
Eosinophils are concentrated in tissues that interface with the external environment, such as the gastrointestinal tract, the thymus, and the lungs. The granules are pre-loaded with potent cationic proteins:
- Major Basic Protein (MBP)
- Eosinophil Cationic Protein (ECP)
- Eosinophil Peroxidase (EPO)
- Eosinophil-Derived Neurotoxin (EDN)
Primary Roles in Parasitic Defense and Homeostasis
The primary function of the eosinophil is host defense against multicellular parasites, particularly helminths. These organisms are too large to be engulfed by standard immune cells like macrophages. Eosinophils bind to the parasite’s surface, often after the helminth has been coated by specific antibodies like Immunoglobulin E (IgE).
Upon activation, the eosinophil releases its granule contents onto the parasite’s external wall (degranulation). Major Basic Protein is highly toxic and disrupts cell membranes. Eosinophil Cationic Protein creates pores in the parasite’s surface, while Eosinophil-Derived Neurotoxin targets genetic material through ribonuclease activity.
Beyond parasitic defense, eosinophils maintain tissue health. They are resident cells in many organs, contributing to tissue integrity and repair. They help regulate gastrointestinal function and participate in tissue remodeling by releasing growth factors.
Eosinophils secrete factors like Transforming Growth Factor-beta (TGF-β) and Vascular Endothelial Growth Factor (VEGF). This promotes the differentiation of fibroblasts and the deposition of extracellular matrix components. This activity supports the regeneration of epithelial surfaces after minor damage, aiding wound healing and structural maintenance.
Eosinophils in Allergic and Inflammatory Disorders
The eosinophil’s granule contents become problematic when the cells are misdirected in response to harmless substances, such as allergens. This activity is a hallmark of Type 2 inflammation, characterized by the production of interleukins, particularly IL-4, IL-5, and IL-13. These promote eosinophil recruitment, survival, and activation.
In conditions like eosinophilic asthma, allergic rhinitis, and atopic dermatitis (eczema), eosinophil degranulation drives chronic inflammation. When toxic cationic proteins are released, they damage the host’s epithelial lining. This leads to chronic symptoms and long-term tissue changes.
Eosinophilic Esophagitis (EoE) is a severe example where the esophagus is densely infiltrated by eosinophils, often due to food allergens. The prolonged release of Major Basic Protein causes inflammation and tissue remodeling. This remodeling involves the thickening of the muscle layer and fibrosis, which can lead to strictures and difficulty swallowing (dysphagia).
The chronic nature of Type 2 inflammatory diseases stems from this cycle of tissue damage. While the release of growth factors like TGF-β is beneficial for wound healing, its continuous release in chronic inflammation promotes fibrosis. This leads to irreversible structural changes, such as airway wall thickening in asthma or esophageal rigidification in EoE.
Clinical Measurement and Management of Eosinophil Activity
The number of eosinophils in the bloodstream is measured using the Absolute Eosinophil Count (AEC). The normal reference range for an AEC in adults is between 30 and 350 cells per microliter. A count consistently exceeding 500 cells per microliter is termed eosinophilia.
A high AEC suggests an underlying allergic disorder, parasitic infection, or an eosinophil-driven disease. Conversely, a low count (eosinopenia), below 30 cells per microliter, can be a temporary side effect of high cortisol levels or corticosteroid use. Eosinophil activity can also be inferred by measuring the levels of released granule proteins, such as ECP, in the blood or sputum.
Management of diseases driven by excessive eosinophil activity traditionally relies on anti-inflammatory agents, most notably corticosteroids. These medications suppress the immune system, reducing the production and activation of eosinophils. However, the long-term use of systemic corticosteroids is associated with undesirable side effects.
Newer treatments focus on targeted molecular pathways. Biologic medications target the Interleukin-5 pathway, the main regulator of eosinophil survival and proliferation. Drugs like mepolizumab and reslizumab are monoclonal antibodies that neutralize the IL-5 cytokine, preventing it from signaling to eosinophils. Benralizumab targets the IL-5 receptor alpha subunit (IL-5Rα) on the eosinophil surface, triggering depletion by natural killer cells through Antibody-Dependent Cellular Cytotoxicity.