Effective antigen presentation to helper T cells by human eosinophils

Farhan, Ruhaifah Kulaib; Vickers, Mark A.; Ghaemmaghami, Amir M.; Hall, Andrew M.; Barker, Robert N.; Walsh, Garry Michael

doi:10.1111/imm.12658

Cited by 33 publications

(24 citation statements)

References 41 publications

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“…Studies in mice and humans demonstrate that antigen and cytokine‐primed eosinophils are capable of functioning as professional antigen‐presenting cells in vitro and in vivo . Eosinophils recruited to the oesophagus in patients with eosinophilic oesophagitis express the antigen presentation markers HLA‐DR and CD80 .…”

Section: Discussionmentioning

confidence: 99%

Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils

et al. 2018

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Intestinal eosinophils are implicated in homeostatic and disease-associated processes, yet the phenotype of intestinal tissue-dwelling eosinophils is poorly defined and their roles in intestinal health or disease remain enigmatic. Here we probed the phenotype and localization of eosinophils constitutively homed to the small intestine of naive mice at baseline, and of antigen-sensitized mice following intestinal challenge. Eosinophils homed to the intestinal lamina propria of naive mice were phenotypically distinguished from autologous blood eosinophils, and constitutively expressed antigen-presenting cell markers, suggesting that intestinal eosinophils, unlike blood eosinophils, may be primed for antigen presentation. We further identified a previously unrecognized resident population of CD11c eosinophils that are recovered with intraepithelial leucocytes, and that are phenotypically distinct from both lamina propria and blood eosinophils. To better visualize intestinal eosinophils in situ, we generated eosinophil reporter mice wherein green fluorescent protein expression is targeted to both granule-delimiting and plasma membranes. Analyses of deconvolved fluorescent z-section image stacks of intestinal tissue sections from eosinophil reporter mice revealed eosinophils within intestinal villi exhibited dendritic morphologies with cellular extensions that often contacted the basement membrane. Using an in vivo model of antigen acquisition in antigen-sensitized mice, we demonstrate that both lamina propria-associated and intraepithelium-associated eosinophils encounter, and are competent to acquire, lumen-derived antigen. Taken together these data provide new foundational insights into the organization and functional potential of intestinal tissue-dwelling eosinophils, including the recognition of different subsets of resident intestinal eosinophils, and constitutive expression of antigen-presenting cell markers.

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Section: Discussionmentioning

confidence: 99%

Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils

et al. 2018

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“…Eosinophils contribute to adaptive immunity through the production of DC and effector T H cell chemoattractants such as EDN, CCL17, CCL22, CXC-chemokine ligand 9 (CXCL9) and CXCL10 (REFS 27,71,72,135,136); and by functioning as antigen-presenting cells 137,138 . Eosinophils can be involved in tumour rejection by normalizing tumour vessels and enhancing the infiltration of CD8 + T cells, owing to eosinophil secretion of IFNγ, TNF, CCL5, CXCL9 and CXCL10 (REF.…”

Section: Eosinophils In Other Host Responsesmentioning

confidence: 99%

Functions of tissue-resident eosinophils

2017

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Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, ‘non-effector’ functions in health and disease.

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“…Upon activation by certain cytokines or other inflammatory stimuli, eosinophils can up-regulate these molecules and stimulate primed CD4 T cell responses in vitro and in vivo. 179,180 Whether eosinophils function as APC at the tumor site remains to be determined.…”

Section: Eosinophils As Accessory Cells In Cancermentioning

confidence: 99%

Eosinophils: The unsung heroes in cancer?

et al. 2017

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Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu. In several neoplasias (e.g., melanoma, gastric, colorectal, oral and prostate cancer) eosinophils play an anti-tumorigenic role, in others (e.g., Hodgkin's lymphoma, cervical carcinoma) have been linked to poor prognosis, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of eosinophils and their mediators could be cancer-dependent. The microlocalization (e.g., peritumoral intratumoral) of eosinophils could be another important aspect in the initiation/progression of solid and hematological tumors. Increasing evidence in experimental models indicates that activation/recruitment of eosinophils could represent a new therapeutic strategy for certain tumors (e.g., melanoma). Many unanswered questions should be addressed before we understand whether eosinophils are an ally, adversary or neutral bystanders in different types of human cancers.

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Effective antigen presentation to helper T cells by human eosinophils

Cited by 33 publications

References 41 publications

Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils

Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils

Functions of tissue-resident eosinophils

Eosinophils: The unsung heroes in cancer?

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