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Medical Journal Reviews

The International Eosinophil Society (IES) selects articles on a monthly basis for their importance to scientists and clinicians interested in the eosinophil. We welcome Medical Journal Review submissions from IES Members for consideration. Your review should be clear, compelling, and appeal to our international membership.

Click here to submit your review and download the submission guidelines here.

April 2024

Eosinophils potentiate anti-bacterial immunity

Article: Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity
Zhou, J., Liu, J., Wang, B. et al.
Signal Transduction and Targeted Therapy, Article No. 43, 28 Feb. 2024

Reviewed by Roopa Hebbandi Nanjundappa, MSc, PhD, Dalhousie University, Halifax, Canada

The generation of memory T cell responses against infections is considered a hallmark of protective immunity. The generation of CD8+ T cell memory relies on several factors including cytokine milieu in the microenvironment, initial CD4+ T cell responses, and the presence of macrophages (Cullen et al., 2019; Son et al., 2021; Lobby et al., 2022). The precise role of eosinophils in CD8+ T cell responses during infections has remained unclear. Therefore, a recent study by Zhou et al. aimed to elucidate the contribution of eosinophils to the generation of memory CD8+ T cell responses using an OVA-expressing Listeria monocytogenes (L.m) infection model via intraperitoneal injections. The study employed both in vitro culture techniques and a mouse model deficient in eosinophils (ΔdblGATA-1) to investigate the role of eosinophils in the generation of L.m-specific memory CD8+ T cells in spleen and mesenteric lymph nodes (MLNs). The findings revealed that eosinophils play a crucial role in enhancing the generation of CD8+ T cell memory to L.m infection, in the spleens but not in the MLNs, thereby providing resistance to reinfection in mice. Mechanistically, eosinophil-derived IL-4 was found to rescue L.m infection-induced JNK/Caspase-3 dependent apoptosis of CD8+ T cells, thus facilitating the establishment of immunological memory against bacterial infection. The involvement of IL-4 was confirmed through both in vitro culture assays and adoptive transfer experiments involving wildtype and IL-4 deficient eosinophils into ΔdblGATA-1 mice.

A major strength of the study lies in the authors' exploration of the previously undefined role of eosinophils in potentiating CD8+ T cell immunological memory in the context of L.m infection. Furthermore, this study opens up new questions: (1) Do transgenic IL-5 mice, which harbor increased eosinophil levels, show heightened CD8+ T cell immunological memory against L.m? (2) Does L.m. infection via oral routes induce similar memory in the gastrointestinal tract (GI), given that eosinophils are abundant in the GI tract lining? (3) Does a similar mechanism exist for other bacterial, viral, and fungal infections? (4) Are there any susceptibilities or compromises in patients receiving eosinophil-depleting therapies to secondary bacterial infections or responses to vaccinations?

Roopa Hebbandi Nanjundappa, MSc, PhD, is an AAI postdoctoral fellow at Dalhousie University. She earned her PhD in Immunology from the University of Calgary, where her research focused on understanding how a gut microbial molecular mimic of pancreatic beta-cell auto-antigen can protect the host from inflammatory bowel disease. Currently, she is investigating the roles of mast cells and eosinophils in Respiratory Syncytial Virus (RSV) infection under the mentorship of Dr. Jean Marshall.

March 2024

Nourishing insights: diet-driven adaptation of eosinophils

Article: Nutrient-Derived Signals Regulate Eosinophil Adaptation to the Small Intestine
Kutyavin, Vassily I, et al.
National Academy of Sciences of the United States of America, vol. 121, no. 5, 25 Jan. 2024

Reviewed by Krishan Chhiba, MD, PhD, Northwestern University, Chicago, United States

Eosinophils are abundant in the small intestines of mice and humans, where nutrients are absorbed. Few studies have examined the effect of diet on eosinophils residing in the small intestine. The authors of this study use BrdU labeling to mark proliferating eosinophils. They show that eosinophils initially enter the tissues near the crypt and migrate from the crypt to the villus of the small intestine. These spatially distinct eosinophils are also noted to be transcriptionally distinct and can be distinguished by their expression of α4β7 (crypt) and CD22 (villus). The authors propose that these changes demonstrate eosinophil adaptation. IL-5, IL-33 and microbiome are not necessary for adaptation. RAR signaling antagonist reduced small intestine eosinophils and preferentially the CD22+ villus-resident eosinophils. Mice that also ate a high-protein diet exhibited an even further reduced eosinophil frequencies, suggesting that the pathways involved are distinct. Finally, the authors show that adoptively transferred of eosinophils still responded to the high-protein diet in host mice suggesting that dietary nutrients are not affecting eosinophil development in the bone marrow. 

While clinical improvement is seen with dietary modification in EGIDs, the mechanism of this effect needs further investigation. This study adds to our understanding of eosinophils by showing how the nutrient microenvironment contributes to the adaptation of eosinophils in the gastrointestinal tract. Efficacy of eosinophil-targeted therapies in EGIDs may relate to the subpopulations of eosinophils in the gastrointestinal tract that are targeted. Further studies in humans are needed.

While reviewing this paper, the following questions come to mind: (1) Are α4β7+ (crypt) and CD22+ (villus) eosinophil subtypes found in humans with EoN during active disease and how do their frequencies change after an amino acid-based elemental diet? (2) Since eosinophil apoptosis is not triggered by direct exposure to high amino acid concentration, is there an intermediary cell type that helps to orchestrate the effect shown in this manuscript? (3) What is the consequence of increased or decreased villus-resident eosinophils on tissue inflammation and disease pathology?, and (4) Will spatial transcriptomics of eosinophils in the small intestine identify even further complexity of the spatial adaptation taking place.

Krishan Chhiba, MD, PhD, is an Allergy and Immunology fellow and post-doctoral researcher at Northwestern University. He obtained his MD and PhD degrees at Northwestern, where he studied the phenotypic and functional plasticity of mast cells and mast cell-targeting therapeutics under the mentorship of Drs. Bruce Bochner and Paul Bryce. He is performing his post-doctoral research in the laboratory of Dr. Fei Li Kuang. His basic science research will focus on defining the roles of eosinophils in eosinophilic gastrointestinal disease and allergic hypersensitivity reactions. He is leveraging advances in eosinophils transcriptomics and proteomics to elucidate the changes underlying the development of peripheral eosinophilia and tissue eosinophilia in humans. Krishan is serving on the IES Scientific Program Committee.

February 2024

Eosinophils identified as a major contributor to bone homeostasis via eosinophil peroxidase activity

Article: Eosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase
Andreev, D., Kachler, K., Liu, M. et al
Nat Commun 15, 1067 (2024)

Reviewed by Nana-Fatima Haruna, PhD Candidate, Northwestern University, Chicago, United States

Only recently has the field of immunology begun to appreciate the functional diversity of eosinophils during steady-state homeostatic conditions. There remains a significant gap in our knowledge of the roles and mechanisms utilized by eosinophils to perform their homeostatic functions in different tissues.

The localization of eosinophils within the bone marrow has been a suspected mechanism utilized by eosinophils to perform homeostatic functions. Within the bone marrow, eosinophils colocalize with plasma cells and contribute to their survival (Chu et al., Nat Immunol. 2011 Feb;12(2):151-9). Similarly, the authors of this paper show localization of eosinophils with osteoclasts within the bone marrow. To completely assess bone formation rate, the authors evaluated osteoclast surface (osteoclast surface per bone surface). Quantification of osteoclast surface and cell number provides information on the bone resorption activity of the cell at a given time. Their data showed a significant reduction in bone mass as well as an increase in osteoclast surface and number in eosinophil-deficient ΔdblGATA mice. IL-5 transgenic mice, displaying hyper-eosinophilic phenotype, showed increased bone mass and reduced osteoclast surface and number, indicating a direct relationship between eosinophils and steady-state bone marrow remodeling.

Bulk RNA seq of osteoclasts co-cultured with eosinophils or eosinophil supernatants revealed downregulation of genes involved in osteoclast signaling while upregulating phagocytosis pathways. Eosinophil heme peroxidase, EPX, is internalized by osteoclast precursors, impairing RANKL-mediated signaling thereby inhibiting osteoclast activation. EPX significantly reduced mitochondrial reactive oxygen species in osteoclast precursors. In vivo mouse experiments showed the ability of EPX to successfully resolve inflammation-associated bone loss by reducing the surface and number of mature osteoclasts, thereby preventing excessive bone resorption by osteoclasts. The authors observed a positive correlation between trabecular bone mass and eosinophil counts as well as eosinophil cationic protein levels in rheumatoid arthritis patients, indicating that eosinophil could also be involved in regulating bone homeostasis in humans.

Taken together, this paper expands the field’s understanding of the homeostatic role of eosinophils within the bone marrow and highlights EPX as a key driver in eosinophil-dependent regulation of bone homeostasis. The study also draws attention to the importance of eosinophil spatial organization within tissue microenvironments in providing insight into their tissue-resident functions.

Nana-fatima Haruna is a Ph.D. candidate under the supervision of Dr. Sergejs Berdnikovs at Northwestern University in Chicago. She is currently investigating eosinophil emergency hematopoiesis at sites of inflammation. Nana is interested in utilizing a systems biology approach to understanding eosinophil biology in health and inflammatory conditions. Before joining the Berdnikovs lab, she worked as an application scientist in a biotech company at the New Jersey Bioscience Center, researching the extracellular matrix and the impact of tissue microenvironment on cell behavior. Nana serves on the IES Outreach and Diversity Committee and the Website/Social Media Committee.

Past Reviews

January 2024

Transcriptomic profiling of the acute mucosal response to local food injections in adults with eosinophilic esophagitis
Reviewed by Eva Gruden, Pharmacist, Medical University of Graz, Austria

December 2023

Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection
Reviewed by Rachael FitzPatrick, PhD Candidate, Reynolds Laboratory at the University of Victoria, Canada

October 2023

Neuromedin U programs eosinophils to promote mucosal immunity of the small intestine
Reviewed by Beth Jacobson, PhD with input from Marc Rothenberg, MD, PhD

Chronic HDM exposure shows time-of-day and sex-based differences in inflammatory response associated with lung circadian clock disruption
Reviewed by Julia Teppan, MSc.Ph.D.Student

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