A tribute to eosinophils from a comparative and evolutionary perspective

The presence of “eosinophilic” or acidophilic blood cells/hemocytes has been recognized as well in various invertebrate species, but it is still unknown whether these are evolutionary precursors to eosinophils in vertebrates.1 Notably, coelacanths, estimated to have evolved 350 million years ago, already had eosinophils.2 There is evidence that neutrophil and eosinophil myeloperoxidase diverged approximately 60 to 70 million years ago, well before mammalian species, suggesting specialization of this unique granulocyte type.1 As evident from Fig 1, eosinophils vary most particularly in the size and appearance of their eosin-stained secondary (specific) granules, for example, the very large granules seen in the crocodile, tortoise, and horse, compared with most other taxa represented here. The “LIAR” (Local Immunity And/or Remodeling/Repair) hypothesis, derived principally from mouse models, expanded understanding of eosinophils beyond end-stage effector cells involved in host defense against parasites and other pathogens.3 In fact, eosinophils or eosinophilic granule–containing hemocytes are crucial in tissue remodeling including involvement in metamorphosis in amphibians and invertebrates, respectively, demonstrating their participation in concerted events in pathways of developmental biology and metabolism, modulation of innate and adaptive immune responses, maintenance of tissue and metabolic homeostasis, and involvement in tissue remodeling and fibrosis in human disease pathogenesis.1,3 However, these findings are contrasted by transgenic mouse models in which the eosinophil lineage was eliminated, but surprisingly no significant clinical abnormalities have been evident in these animals under specific pathogen-free vivarium conditions.1 Given their involvement in complex physiological processes, the question of the eosinophils’ continuous involvement in ongoing evolutionary processes across taxa seems logical and intriguing.1,4 In human medicine, eosinophils are a focus of targeted therapeutics and basic investigations, including functions in tissue homeostasis in health and roles in disease. [...]to the mouse, eosinophil-targeting biologics that partially or more fully deplete eosinophils have thus far proven safe across a range of eosinophilic inflammatory disorders, with no evidence of increased infections, malignancies, or other pathological conditions, for example, in patients with asthma and hypereosinophilic syndrome (HES) treated with anti–IL-5