Biology of the eosinophil

Abstract

In this review, we aim to put in perspective the biology of a multifunctional leukocyte, the eosinophil, by placing it in the context of innate and adaptive immune responses. Eosinophils have a unique contribution in initiating inflammatory and adaptive responses, due to their bidirectional interactions with dendritic cells and T cells, as well as their large panel of secreted cytokines and soluble mediators. The mechanisms and consequences of eosinophil responses in experimental inflammatory models and human diseases are discussed.

Figure 1. From the hematopoietic stem cell to the mature eosinophil

Eosinophils develop in the bone marrow. Transcription factor (such as Δdbl-GATA-1) and cytokines (such as IL-5, IL-3 and GM-CSF) are essential for their differentiation from an hematopoietic stem cell into the mature eosinophil. Once mature, IL-5 controls the eosinophil migration from the bone marrow to the blood. At baseline, eosinophils localize in the thymus, GI tract, uterus and mammary gland. Eosinophils are able to express and to secrete, at baseline or upon stimulation, a large variety of mediators (cytokines, granule proteins, lipid mediators). Eosinophils are putative antigen presenting cells and play a role in mast cell activation, T cell communication and function.

Figure 2. Eosinophil trafficking

Once mature in the bone marrow, IL-5 controls the migration of eosinophils into the blood. At baseline, eotaxin-1 drives eosinophils in the thymus, uterus, mammary gland and gastrointestinal tract. Eosinophils express adhesion molecules (integrins) that allow attachment to the endothelial surface (VCAM-1, MadCAM-1, ICAM-1). Tissue chemokine expression allows the formation of a gradient chemotactic that guide the eosinophils in the tissue. In Th2 diseases, Th2 cytokines increase chemokine expression. In the asthmatic lung, eotaxin-1, 2 and -3 are increased and/or involved in chemotaxis of eosinophils, as well as other molecules such as LTB4. In the gastrointestinal tract eotaxin-3 is a key player in the eosinophilia observed in eosinophilic esophagitis while eotaxin-1 has been shown to be involved in the lower gastrointestinal eosinophilic diseases.

Figure 3. Eosinophil function

Eosinophils are believed to have a beneficial role in helminthic infection while no direct evidence was provided in the eosinophil depleted mice. Ribonuclease in granules display anti viral property on RNA virus such as RSV. Eosinophils are able to bind to fungal wall via their β2 integrin chain. Finally, DNA traps possess antibacterial activities. Eosinophils are involved in the pathological features of several diseases. In asthma, using eosinophil depleted mice (Δdbl-GATA-1 and PHIL) eosinophils have been shown involved in AHR, mucus production, TH2 cytokine production and collagen deposition. The role of eosinophils in EGID and HES might lead to tissue damage but needs to be better studied.