Eosinophils in innate immunity: an evolving story

Abstract

Eosinophils are innate immune leukocytes found in relatively low numbers within the blood. Terminal effector functions of eosinophils, deriving from their capacity to release their content of tissue-destructive cationic proteins, have historically been considered primary effector mechanisms against specific parasites, and are likewise implicated in tissue damage accompanying allergic responses such as asthma. However, the past decade has seen dramatic advancements in the field of eosinophil immunobiology, revealing eosinophils to also be key participants in many other facets of innate immunity, from bridging innate and adaptive immune responses to orchestrating tissue remodeling events. Here, we review the multifaceted functions of eosinophils in innate immunity that are currently known, and discuss new avenues in this evolving story.

Fig. 1

Preformed cytokines, chemokines and growth factors are secreted from intracellular granules through piecemeal degranulation. Transport of granule-derived proteins occurs by the mechanism of piecemeal degran-ulation, involving budding of small spherical and elongated tubular (EoSV) vesicles from intracellular granules, which then traffic to the plasma membrane for mediator release. a Activation of eosinophils causes mobilization of intracellular granule cores and loss of granule contents, along with an increase in vesicular traffic (vesicles pseudocol-ored in purple). b Intragranular membranous subcompartments (pseu-docolored in purple) are often visualized in conjunction with a mobilized core prior to the emergence of spherical and tubular sombrero vesicles. c Some EoSVs exhibit membrane-bound contents, representing receptor-dependent chaperoning of granule-derived cytokines. d Vesicular contents are released extracellularly following fusion with the plasma membrane. EoSV Eosinophil sombrero vesicle, Gr granule, Nu nucleus

Fig. 2

Innate immune functions of eosinophils and their contributions to host defense. Innate immune functions of eosinophils include terminal effector functions (a–d), immunomodulation (e) and tissue repair and remodeling (f). a Eosinophilic interactions with extracellular virons result in destruction by eosinophil-associated ribonu-cleases. b Cross-linking of FcγII receptors by helminth-bound IgG1 and IgG3 mediate eosinophil activation and degranulation of helminth-destructive cationic proteins. c LPS-stimulated eosinophils release extracellular traps, containing mitochondrial DNA and granule-derived proteins, to eradicate bacterial infiltration. Bacteria can also be removed by secretion of granule-derived proteins and phagocytosis. d CD11b integrin- mediated adherence of β-glucan induces vesicular release of EDN in response to fungal infestation. e Eosinophils act as immunomodulators and direct T helper cell differentiation through secretion of immune-polarizing cytokines and functioning as professional antigen presenting cells. f Eosinophils secrete numerous mediators with effects on tissue remodeling, including TGFβ, IL-13 and MMPs

Fig. 3

Innate immune functions of gastrointestinal eosinophils. a Cross-linking of membrane bound IgA receptors by secretory IgA linked to bacterial microbes elicits secretion of granule-derived proteins by eosinophils. b In response to epithelial damage, eosinophils secrete multiple mediators (including FGF-2 and TGF-β) to promote tissue repair and remodeling, maintaining the integrity of the epithelial barrier. c Eosinophils may be stimulated to secrete mitochondrial DNA and granule derived proteins in the form of an extracellular trap for infiltrating bacteria. d Eosinophils can be found in association with lymphocytes within gastrointestinal Peyer’s patches