Eosinophils: multifaceted biological properties and roles in health and disease

Abstract

Eosinophils are leukocytes resident in mucosal tissues. During T-helper 2 (Th2)-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with proinflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field.

Figure 1

Deposition of EDN in esophageal tissue from patients with eosinophilic esophagitis (EoE). Esophageal biopsy specimens from two separate EoE patients (A and B) were stained with rabbit anti-human EDN antibody followed by FITC-conjugated goat anti-rabbit IgG. Wide spread diffuse extracellular EDN is observed throughout the esophageal epithelium, in particular on the luminal surface and in the superficial mucosa. Arrows indicate intact eosinophils. Original magnification; ×160 (A) and ×400 (B).

Figure 2

Differential responses of mouse and human eosinophils to stimuli. Panels A and B show superoxide production induced by immobilized IgGs, PAF, IL-5 or eotaxin in human and IL-5 transgenic mouse eosinophils, respectively. Human eosinophils were stimulated with immobilized IgGs [wells precoated with 100 µg/ml human (h)IgG1, mouse (m)IgG1, mIgG2a or mIgG2b], 1 µM PAF, 5 ng/ml recombinant hIL-5, 50 ng/ml hEotaxin, or 10 ng/ml PMA. Peritoneal lavage mouse eosinophils were stimulated similarly except recombinant mIL-5 and mEotaxin were used at the same concentrations. Superoxide production was measured by reduction of cytochrome c. Results are means ± SEM of three experiments. Panels C and D depict the morphology of human and mouse eosinophils stimulated with immobilized hIgG1 and mIgG2a, respectively. Original magnification; ×400.

Figure 3

Multifaceted functions of eosinophils. Functional properties of eosinophil can be divided into at least three stages including resting, partial activation and full activation. Different types of immunological stimuli (or absence of stimuli) trigger production and release of different molecules by eosinophils. Accordingly, eosinophils may affect tissue development, homeostasis and repair, regulate the immune responses and exert pro-inflammatory effector functions. Eosinophil survival and death is controlled similarly by stimuli and tissue envi