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Eosinophils are the second most abundant granulocyte and account for 1–3% of circulating leukocytes and ~6% in the bone marrow. They provide host response to parasitic infections and allergic disease. During infection they release cationic proteins stored in cytoplasmic granules by degranulation. In addition, eosinophils release cytokines, including IL-10 and IL-4, to modulate the immune response.
Eosinophils are the poster child for allergic inflammation and were long solely defined by their contribution to allergy induced airway remodeling and parasite clearance. Like neutrophils, eosinophils arise from a committed eosinophil precursor (mouse: Lin- Sca- ckit lo CD34+ IL-5Rα+ Siglec-F TSLRP ST2; human: Lin- IL5-Rα+ CD34+ CD38+ IL-3Rα+ CD45RA-). Eosinophil differentiation from the precursor is dependent on IL-5 and aided by IL-33 and GM-CSF. Key transcription factors contributing to eosinophil linage include GATA-1, Helios, C/EBPε, Aiolos, and XBP-1. Terminally differentiated eosinophils leave the bone marrow and enter the periphery through the blood, mediated by β1 and β2 integrins. In the periphery, eosinophils survive only a few days but during an ongoing inflammation, this can extend to weeks. While some eosinophils can be found in the spleen and lung (~1.5% of all CD45+), the majority accumulates in the gastrointestinal tract and other sites with high epithelial turnover or stem cell activity like thymus or bone marrow.
During inflammation, eosinophils migrate to the site of inflammation, involving similar mechanisms as neutrophils, adhering to endothelial cells followed by diapedesis into the interstitial space after an injury. Mediated by chemotaxis, eosinophils follow eotaxin signals like a breadcrumb trace. Conspicuously, humans express eotaxin 1-3 (CCL11, CCL24, CCL26) while mice only express eotaxin 1 (CCL11) and 2 (CCL24). The signals that mediate eosinophil homing in steady state are less well understood.
Eosinophils’ hallmark innate response is releasing their microbicidal content by degranulation, which (at least in humans) can either happen in a contact dependent manner (for example, directed against macro-pathogens like worms), by piecemeal secretion (delivering specific proteins as cytokines for excretion) or, similar to neutrophils by expelling their protein studded chromatin as a consequence of cytolysis or eosinophil extracellular traps (EET) formation. Eosinophil granule products such as Major Basic Protein (MBP) or TGFβ have been shown to be involved in asthmatic airway remodeling and airway hyperresponsiveness.
The fact that eosinophils have been conserved throughout evolution and populate various tissues in steady state relays their importance in homeostasis. Despite their relatively low numbers (~1–3% of circulating leukocytes, 6% in BM), recent years have shown that eosinophils indeed play a role in tissue development, tissue remodeling and repair, as well as influencing the adaptive immune response. In particular, release of IL-4 and IL-13 driving TH2 responses in tissues seems to depend on resident eosinophils. In addition, eosinophils can produce vast amounts of IL-10, IL-8, and GM-CSF to attract neutrophils. Intestinal eosinophils regulate secretion of mucosal IgA, most likely via production of TGFβ and IL-1α. Eosinophils can contribute to adaptive immunity by either functioning as antigen presenting cells, or by secreting cytokines and chemokines attracting dendritic cells and effector T cells.
Blood eosinophils or disease associated eosinophils and tissue resident eosinophils differ regarding surface marker expression, which raised the question if these populations constitute different subsets. For example, lung resident eosinophils display a Siglec-F int CD101Low CD62+ phenotype and seem to have regulatory function in contrast to recruited eosinophils appearing as Siglec-Fhigh CD101high CD62neg. In the intestine where the mucosa undergoes constant epithelial turnover, eosinophils constitutively express CD11c, Ly6G, and CD44. In lung resident eosinophils however, these markers are only expressed during development or airway remodeling after injury. Thus, there is evidence that eosinophil heterogeneity is not just mediated by the state of maturation but can also be influenced by location (organ or organ compartment) and morphogenetic activity on site. Finally, as type 2 immune responses are associated with tissue (re)modeling and repair, eosinophils in this context are referred to as Type 2 eosinophils (mostly epithelial, SiglecFhigh) and represent most eosinophils in the bronchoalveolar-lavage fluid. On the other hand, eosinophils involved in acute or host defense-related inflammation are generally denoted as Type 1 eosinophils (mostly stromal, Siglec-F int).
The most accessible source for eosinophils in human and mice is blood, while the highest number would be found in bone marrow. Tissue-resident eosinophils can be obtained from most tissues by digesting with tissue appropriate proteases. Another source for eosinophils is bronchoalveolar-lavage fluid obtained from mice in allergic asthma models. In human subjects and mice, eosinophils stain positive for IL-5Rα, CCR3, Siglec-8 (human)/Siglec-F (mice), EMR1 (human)/F4/80 (mice), and CD11b and are characterized by a high side scatter (SSC) in flow cytometry. However, while CCR3 is specific for eosinophils in mice, in humans it can also be expressed by T cells. On the other hand, in mice Siglec-F is expressed by eosinophils and alveolar macrophages, while its human counterpart Siglec-8 is present on eosinophils and mast cells.
Cell subtype | Marker | Localization | Species |
---|---|---|---|
Pan-granulocytes | CD11b | Surface | Human and mouse |
CD13 | Surface | Human | |
CD15 | Surface | Human | |
CD16/32 | Surface | Mouse | |
CD32 | Surface | Human | |
CD33 | Surface | Human | |
Eosinophils | MBPs | Secreted | Human and mouse |
CD193 (CCR3) | Surface | Key phenotyping marker: Human and mouse | |
CD170 (SiglecF) | Surface | Key phenotyping marker: Mouse | |
EDN | Secreted | Human | |
EPX | Secreted | Human and mouse | |
CD9 | Surface | Human and mouse | |
CD15 | Surface | Human and mouse | |
CD24 | Surface | Human and mouse | |
CD35 | Surface | Human and mouse | |
CD43 | Surface | Human and mouse | |
CD64 | Surface | Human and mouse | |
CD116 | Surface | Human and mouse | |
CD123 | Surface | Human and mouse | |
CD125 | Surface | Key phenotyping marker: Human and mouse | |
CD126 | Surface | Human and mouse | |
CD244 | Surface | Human and mouse | |
FceR1 | Surface | Human and mouse |
CD193 is a member of the seven transmembrane G-protein coupled receptor (GPCR) family, and is a high affinity chemokine receptor for the chemokines eotaxin-1 (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), and MCP-4 (CCL13), but has also been reported to bind RANTES, MCP-3, and MCP-4. CD193 is highly expressed on the surface of eosinophils and is the key eosinophil chemokine receptor responsible for the regulation of eosinophil migration and function. In addition to eosinophils, CD193 is also expressed on CD4+ TH2 cells, basophils, mast cells, mononuclear phagocytes, platelets, CD34+ hematopoietic progenitors, and airway epithelial cells.
Figure 3. Identification of human eosinophils by flow cytometry using cellular marker, CD193 (CCR3). Normal human peripheral blood cells were stained with Anti-Human CD16 FITC (Cat. No. 11-0168-42) and Mouse IgG2b K Isotype Control PE (Cat. No. 12-4732-81) (left) or Anti-Human CD193 (CCR3) PE (right) (Cat. No. 12-1939-42). Cells in the granulocyte gate were used for analysis.
Siglec F is a cell surface lectin belonging to the Ig superfamily that binds glycoconjugates containing sialic acids that are commonly found on various cell types. It is expressed mostly on eosinophils and alveolar macrophages, and lower levels of this receptor have also been reported on immature myelomonocytic cells. Mouse Siglec F is a functional ortholog of human Siglec 8. However, unlike human Siglec 8, mouse Siglec F is not expressed on mast cells.
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Overview of basophil cells
Rarest of circulating granulocytes that release histamines.
Immune Cell Guide
Find detailed marker information for immune cell types and subtypes.
Overview of mast cells
Mast cells are predominantly tissue-resident granulocytes that, along with basophils, play a key role in allergy and anaphylaxis.
Protocols for Immunology
Discover protocols for various applications to study immunology.
For Research Use Only. Not for use in diagnostic procedures.