What happens when the body is invaded by viruses, fungi, bacteria, and parasites? A small group of white blood cells, known as eosinophils, gear into action as the first line of defence [1]. They were characterized by Paul Ehrlich in 1879 who discovered them with a technique that employed eosin, a synthetic, acid-loving dye, that turns bright red after binding to granular cells. Thus, he named these cells ‘eosinophils’ after their eosin-loving property. He also observed that the number of eosinophils in blood increased in response to infection and diseases such as asthma. Even though they constitute less than 5% of white blood cells [2], they are involved in diverse functions, including adaptive and innate immunity [3].
Where do they reside?
They are derived from progenitor stem cells in the bone marrow, as well as progenitor cells in other tissues, such as the lungs, in response to inflammation [4]. They migrate from the bone marrow to blood where they exist for only a short period of time. On the other hand, eosinophils that migrate to other tissues e.g. in the lung can survive for up to two weeks [1]. Eosinophils are found in the thymus, gastrointestinal tract, uterus, and mammary gland, under normal conditions, where they play a role in unexpected functions such as organ development, metabolism, and tissue repair [1, 5].
Detecting and destroying pathogens
Eosinophils have a unique structure, with a two-lobed nucleus and large cytoplasmic granules that store lipid mediators, cytokines, chemokines, and cytotoxic granule proteins. These cytotoxic granule proteins are key to their pathogen-fighting abilities. For example, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) can fight parasites, viruses, and bacteria [6]. Similar to white blood cells, they also possess pattern-recognition receptors, such as toll-like receptors, through which they can recognize pathogens and damaged cells [7]. In fact, eosinophils have receptors for a variety of pathogens including coronavirus, polio, and measles [8]. However, unlike other white blood cells, eosinophils also have IL-5 receptors, CC-chemokine receptor 3 (CCR3) and sialic acid-binding immunoglobulin-like lectin 8 (SIGLEC-8) receptors which affect various aspects of their function [1]. IL-5 is important for eosinophil differentiation and maturation and can be utilized to target eosinophils for the treatment of diseases caused by eosinophil dysfunction. Additionally, SIGLEC-8 which has been implicated in the apoptosis of eosinophils is being investigated as a potential target for drugs as well [9]. Still, questions remain about the function of these receptors.
The expression of pattern-recognition receptors by eosinophils allows them to detect and respond to pathogen invasion by releasing cytotoxic granule proteins to kill pathogens, as well as pro-inflammatory mediators such as cytokines and chemokines. These cytokines and chemokines can modulate eosinophil activity in a variety of ways, such as facilitating the infiltration of eosinophils to the site of inflammation and recruiting T cells. On the other hand, excess recruitment of eosinophils can worsen inflammation and tissue damage while fighting off pathogens. Thus, they are associated with disease pathogenesis as well. They can also respond to damaged cells through receptors for damage-associated molecular patterns, thus playing an active role in innate immunity [7].
Teaming up with immune cells
In addition to their remarkable ability to fight a variety of pathogens, eosinophils are also able to play a vital role in adaptive immunity, a feature that has attracted more interest in recent years. It was shown that eosinophils interact with other lymphocytes in a bidirectional manner to regulate immune functions [1]. Even though they are not professional antigen-presenting cells, they can detect and process antigens belonging to pathogens. Eosinophils utilize receptors on their cell membranes for major histocompatibility complex (MHC) class II molecules and the co-stimulatory molecules CD80 and CD86 to present antigens to T cells. For example, a study has shown that eosinophils initiate T cell proliferation by presenting them with antigens in the presence of rhinovirus [10]. Additionally, T cells release cytokines such as IL-5 which has been shown to recruit eosinophils [11].
Moreover, eosinophils can also recruit other immune cells such as dendritic cells, mast cells, B cells, neutrophils, and basophils [12]. In fact, the protein, eosinophil-derived neurotoxin (EDN) found in granules, has been shown to initiate an immune response by type II helper T cells after exposure to allergens by activating dendritic cells [13, 14]. The recruitment of immune cells leads to the release of pro-inflammatory cytokines, such as IL-4 and IL-5, which further engages eosinophils, thus initiating a strong defence against pathogens. Therefore, the interactions between eosinophils and immune cells play a critical role in adaptive immunity [1].
Eosinophils in disease: can too much be a bad thing?
In addition to their involvement in fighting pathogens, eosinophils also play a role in the pathogenesis of diseases such as asthma, respiratory allergies, eosinophilic gastrointestinal diseases, and hypereosinophilic syndromes [4]. When the concentration of eosinophils in the blood increases over a certain amount (>1,500 eosinophils per mm3), it leads to negative consequences in the body. This disorder is known as hypereosinophilic syndrome which can lead to multisystem organ damage. The reason for this increase in eosinophil concentration varies. This syndrome develops in patients with untreated parasitic infections, auto-immune disorders, and other chronic infections [8]. The cytokine IL-5, which is important for eosinophil development, is targeted in treatments for hypereosinophilic syndromes. The current treatment option utilizes an anti-IL-5 agent, which causes depletion of eosinophils concentration. However, further research into the pathogenesis of hypereosinophilic syndrome is necessary for better treatment outcomes for patients [15].
Recognizing and appreciating the labs working in this space
- Hans Carl Hasselbalch lab, Department of Hematology, Zealand University Hospital, Roskilde, Denmark https://www.researchgate.net/profile/Hans-Hasselbalch
- A B Kay lab, Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK
- Helene F. Rosenberg lab, Laboratory of Allergic Diseases, National Institutes of Health, Maryland, USA https://www.researchgate.net/profile/Helene-Rosenberg
- Rothenberg CURED Lab, Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA https://www.cincinnatichildrens.org/research/divisions/a/allergy-immunology/labs/rothenberg , Facebook: RothenbergEosinophilicLab, YouTube: https://www.youtube.com/channel/UCrT1RJErUuX7tg9AVWtLERg
- Lars-Olaf Cardell lab, Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden, https://ki.se/en/people/lars-olaf-cardell
- Bruce S Bochner lab, Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Illinois, USA, https://www.feinberg.northwestern.edu/faculty-profiles/az/profile.html?xid=28140
- Elizabeth A. Jacobsen lab, Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Arizona, USA. https://www.mayo.edu/research/faculty/jacobsen-elizabeth-a-ph-d/bio-00093835
- Weller lab, Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts, USA, https://www.bidmc.org/research/research-by-department/medicine/allergy-and-inflammation/laboratories/weller-lab
- James Paulson lab, Department of Molecular Medicine, Scripps Research Institute, La Jolla, California, USA, https://www.scripps.edu/paulson/ , Twitter: https://x.com/jcpjim
- Steven Jules Ackerman lab, Department of Biochemistry and Molecular Genetics, The University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA, https://chicago.medicine.uic.edu/bmg/profiles/ackerman-steven/ , LinkedIn: https://www.linkedin.com/in/steven-ackerman-68956921/
References
- Ravin, K. A., and M. Loy. “The Eosinophil in Infection.” Clin Rev Allergy Immunol 50 2 (2016): 214–27.
- Bjerrum, O. W., et al. “Association of the Blood Eosinophil Count with End-Organ Symptoms.” Ann Med Surg (Lond) 45 (2019): 11–18.
- Kay, A. B. “The Early History of the Eosinophil.” Clin Exp Allergy 45 3 (2015): 575–82.
- Rosenberg, H. F., K. D. Dyer, and P. S. Foster. “Eosinophils: Changing Perspectives in Health and Disease.” Nat Rev Immunol 13 1 (2013): 9–22.
- Blanchard, C., and M. E. Rothenberg. “Biology of the Eosinophil.” Adv Immunol 101 (2009): 81–121.
- Rosenberg, H. F., and J. B. Domachowske. “Eosinophils, Ribonucleases and Host Defense: Solving the Puzzle.” Immunol Res 20 3 (1999): 261–74.
- Kvarnhammar, A. M., and L. O. Cardell. “Pattern-Recognition Receptors in Human Eosinophils.” Immunology 136 1 (2012): 11–20.
- Valent, P., et al. “Eosinophils and Eosinophil-Associated Disorders: Immunological, Clinical, and Molecular Complexity.” Semin Immunopathol 43 3 (2021): 423–38.
- Kiwamoto, Takumi et al. “Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions.” Pharmacology & therapeutics vol. 135,3 (2012): 327–36.
- Handzel, Z. T., et al. “Eosinophils Bind Rhinovirus and Activate Virus-Specific T Cells.” J Immunol 160 3 (1998): 1279–84.
- Sabin, E. A., M. A. Kopf, and E. J. Pearce. “Schistosoma Mansoni Egg-Induced Early Il-4 Production Is Dependent Upon Il-5 and Eosinophils.” J Exp Med 184 5 (1996): 1871–8.
- Akuthota, P., et al. “Immunoregulatory Roles of Eosinophils: A New Look at a Familiar Cell.” Clin Exp Allergy 38 8 (2008): 1254–63.
- Yang, D., et al. “Eosinophil-Derived Neurotoxin Acts as an Alarmin to Activate the Tlr2-Myd88 Signal Pathway in Dendritic Cells and Enhances Th2 Immune Responses.” J Exp Med 205 1 (2008): 79–90.
- Jacobsen, E. A., et al. “Eosinophils Regulate Dendritic Cells and Th2 Pulmonary Immune Responses Following Allergen Provocation.” J Immunol 187 11 (2011): 6059–68.
- Ackerman, S. J., and B. S. Bochner. “Mechanisms of Eosinophilia in the Pathogenesis of Hypereosinophilic Disorders.” Immunol Allergy Clin North Am 27 3 (2007): 357–75.
About the author:
Dr. Nowrin Ahmed
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Nowrin Ahmed has a PhD in Behavioral and Neural Sciences from Rutgers University-Newark (NJ, USA) where she studied the interactions between the midline thalamus and the amygdala. Currently, she is a post-doctoral fellow at Rutgers University — Newark where she is studying amygdala circuits. Dr. Nowrin enjoys sharing the beauty of science with diverse audiences.
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Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
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Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
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The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
