Human versus mouse eosinophils: “That which we call an eosinophil, by any other name would stain as red”

Abstract

The respective life histories of humans and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiological pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils and/or their effector functions. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide the experimental details, comparing and contrasting eosinophils and eosinophil effector functions in humans vs. mice. In particular, our review will provide a summation and an easy to use reference guide to important studies demonstrating that while differences exist, more often than not their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function, but instead, species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients.

Lung-resident eosinophils represent a distinct regulatory eosinophil subset

“…The presence of such a nucleus in mouse eosinophils is considered a sign of cell immaturity (66,67), suggesting that pulmonary rEos retain an immature phenotype when spreading into the lungs. Using histochemistry, we further showed that lung rEos were located in the parenchyma, which contrasts with the localization of eosinophils in asthma, in which eosinophils are classically thought to infiltrate the peribronchial area (68).…”

Cys-Leukotrienes Promote Fibrosis in a Mouse Model of Eosinophil-Mediated Respiratory Inflammation

“…We recognize that the use of Th2-polarized chronic inflammatory mice that are specifically engineered to understand the shortterm/long-term consequences of pulmonary eosinophil activities is limited as a model of lung dysfunction characteristic of human respiratory disease. Instead, our goal was a reductionist approach to understanding mechanisms potentially mediating eosinophil activities during Th2-driven inflammatory events, which we have suggested are likely shared between humans and mice (28). Thus, if further studies suggest that our observations in mice are translatable to patients with asthma, this result would have significant implications by suggesting that the chronic presence of eosinophils in the lungs of some patients with asthma may elicit sustained expression of pulmonary cys-leukotrienes and, in turn, progressive lung fibrosis.…”

Eosinophils promote inducible NOS–mediated lung allograft acceptance

“…Post-hoc analysis of differences and comparison of differences between pairs of data were performed with the Wilcoxon rank test and the Mann-Whitney U test for paired and unpaired observations, respectively. Figure 2B) (13,14). Romanowsky staining of flow cytometrically sorted cells demonstrated an intense eosinophilic cytoplasmic staining, with a characteristic eosinophil-defining ring-shaped nucleus ( Figure 2C).…”