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  • Review Article
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Eosinophils: changing perspectives in health and disease

Nature Reviews Immunology volume 13, pages 9–22 (2013)Cite this article

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Key Points

  • Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have provided a more sophisticated understanding of eosinophil effector functions and a more nuanced view of their contributions to the pathogenesis of various diseases, including asthma and respiratory allergies, eosinophilic gastrointestinal diseases, hypereosinophilic syndromes and parasitic infection.

  • Eosinophils are granulocytes that develop in the bone marrow from pluripotent progenitors in response to cytokines, such as interleukin-5 (IL-5), IL-3 and granulocyte–macrophage colony-stimulating factor (GM-CSF). Mature eosinophils are released into the peripheral blood and enter tissues in response to cooperative signalling between IL-5 and eotaxin family chemokines.

  • Eosinophils in peripheral blood and tissues are uniquely identified by their bilobed nuclei, their large specific granules that store cytokines, cationic proteins and enzymes, and their expression of the IL-5 receptor and CC-chemokine receptor 3 (CCR3). In addition, the receptors sialic acid-binding immunoglobulin-like lectin 8 (SIGLEC-8) and SIGLEC-F are expressed by human and mouse eosinophils, respectively.

  • IL-5 has a central and profound role in all aspects of eosinophil development, activation and survival. IL-5 is produced by T helper 2 (TH2) cells, and more recently the contributions of the epithelium-derived innate cytokines thymic stromal lymphopoietin (TSLP), IL-25 and IL-33 in promoting eosinophilia via the induction of IL-5 have also been recognized.

  • Although eosinophil responses are influenced by cytokines produced by T cells, eosinophils in turn modulate the functions of B and T cells. Eosinophils also communicate with a range of innate immune cells (such as mast cells, dendritic cells, macrophages and neutrophils). Eosinophils serve to bridge innate and adaptive immunity by regulating the production of chemoattractants and cytokines (including CC-chemokine ligand 17 (CCL17), CCL22, a proliferation-inducing ligand (APRIL) and IL-6) and via antigen presentation.

  • Both successful and unsuccessful attempts to target eosinophils have yielded remarkable insights into their contribution to disease pathogenesis. Many eosinophil-associated inflammatory conditions have been shown to be heterogeneous in nature. As such, successful therapeutic strategies will depend on the correlation of disease activity with dysregulated eosinophil function as well as the identification of the crucial molecules that regulate eosinophil accumulation in the affected tissues.

Abstract

Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular pathways that control the development, trafficking and degranulation of eosinophils have improved our understanding of the immunomodulatory functions of these cells and their roles in promoting homeostasis. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of different diseases, including asthma and primary hypereosinophilic syndromes, and have also provided us with a more complete appreciation of the activities of these cells during parasitic infection.

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Figure 1: The eosinophil.
Figure 2: Cellular features of eosinophils.
Figure 3: Eosinophils modulate the function of other leukocytes.

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Acknowledgements

The authors thank R. Dreyfuss (Medical Arts Branch, Office of the Director, US National Institutes of Health (NIH)) for photographic images and E. R. Fischer (Research Technologies Section, Rocky Mountain Laboratories, US National Institute of Allergy and Infectious Diseases (NIAID), NIH) for preparing the transmission electron micrograph of the mouse eosinophil. H.F.R. receives funding from the NIAID Division of Intramural Research (grants AI000941 and AI000943); P.S.F. receives funding from the National Health and Medical Research Council of Australia and fellowship support from the Harvard Club of Australia.

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  1. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Helene F. Rosenberg & Kimberly D. Dyer

  2. Priority Research Centre for Asthma and Respiratory Diseases, Kookaburra Way, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, 2300, NSW, Australia

    Paul S. Foster

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Disorders associated with eosinophilia and/or eosinophil accumulation in organs and tissues (PDF 100 kb)

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Glossary

Innate lymphoid cells

Cells that produce cytokines typically attributed to T helper cell subsets (for example, IL-5) but that have no rearranged antigen-specific receptors.

Alarmin

A term used to describe endogenous molecules that interact with pattern- recognition receptors and thereby signal danger to the host. These molecules are typically released from necrotic cells and complement the function of the more familiar pathogen-associated molecular patterns. Examples discussed in this Review include HMGB1 and IL-33. Another name for an alarmin is a damage- or danger-associated molecular pattern.

Cytolytic degranulation

A mechanism through which eosinophils lyse, thereby releasing either free granule proteins or fully intact granules. This renders the cells non-viable. Intact granules released in this manner can respond to physiological secretagogues.

Piecemeal degranulation

A mechanism through which eosinophils (as well as basophils and mast cells) release specific mediators from cytoplasmic granules by transporting them to the cell surface in membrane-bound cytoplasmic vesicles. The eosinophils remain viable and fully responsive to subsequent stimuli.

Secretagogues

Substances that induce the secretion of another substance from a cell or storage granule.

Promyelocyte

A cell in the bone marrow that has differentiated from a haematopoietic stem cell and that will ultimately generate mature granulocytes, including neutrophils, basophils and eosinophils. A promyelocyte can be identified in bone marrow smears as a relatively large cell with a full, non-condensed nucleus and lineage-specific cytoplasmic granules.

Common myeloid progenitors

(CMPs). In current models of haematopoiesis, the most primitive cells are multipotent, self-renewing haematopoietic stem cells. By definition, CMPs are the subset of progenitor cells that are capable of generating all myeloid cells (that is, monocytes, macrophages, dendritic cells, erythrocytes, megakaryocytes, platelets, basophils, eosinophils and neutrophils) under appropriate cytokine stimulation, but that are no longer capable of generating cells of the lymphoid lineages (such as B cells, T cells and NK cells).

Granulocyte–macrophage progenitors

(GMPs). By definition, GMPs are the subset of progenitor cells that are capable of generating monocytes, macrophages and all granulocyte lineages (that is, basophils, eosinophils and neutrophils), but not the other lineages. However, as noted in the text, human eosinophils are not derived from the cells currently identified as GMPs.

Alternatively activated macrophages

One of the major differences between these cells and classically activated macrophages is that these macrophages are not primed with IFN. Instead, alternatively activated macrophages are stimulated by TH2-type cytokines (such as IL-4 or IL-13) and present soluble antigens to T cells. Alternatively activated macrophages release CCL17, CCL18, CCL22, IL-10, TGF, YM1, YM2 and RELM, and they characteristically function to promote the resolution of inflammation.

Nurse cells

As used in this Review, this term refers to skeletal muscle cells that have been infected with the larval forms of Trichinella species parasites. A capillary network forms around the nurse cells, which provides crucial support for the parasites as they develop.

Neutrophil extracellular traps

(NETs). Fibrous networks that are released into the extracellular environment by neutrophils. They are composed mainly of DNA, but also contain proteins from neutrophil granules. NETs act as a mesh that traps microorganisms and exposes them to neutrophil-derived effector molecules.

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Rosenberg, H., Dyer, K. & Foster, P. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13, 9–22 (2013). https://doi.org/10.1038/nri3341

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