Abstract

Dysregulation of the immune system is associated with many pathologies, including cardiovascular diseases, diabetes, and cancer. To date, the most commonly used models in biomedical research are rodents, and despite the various advantages they offer, their use also raises numerous drawbacks. Recently, another in vivo model, the chicken embryo and its chorioallantoic membrane, has re-emerged for various applications. This model has many benefits compared to other classical models, as it is cost-effective, time-efficient, and easier to use. In this review, we explain how the chicken embryo can be used as a model for immune-based studies, as it gradually develops an embryonic immune system, yet which is functionally similar to humans’. We mainly aim to describe the avian immune system, highlighting the differences and similarities with the human immune system, including the repertoire of lymphoid tissues, immune cells, and other key features. We also describe the general in ovo immune ontogeny. In conclusion, we expect that this review will help future studies better tailor their use of the chicken embryo model for testing specific experimental hypotheses or performing preclinical testing.

Highlights

  • The immune system has vital functions for the organism, from defense to homeostasis

  • Many studies have been done in chickens, where administration of LPS has been shown to cause a significant influx of heterophils, and to increase the release of pro-inflammatory mediators such as IL-1b, IL-6, IL-8, TNF-a, iNOS, and COX-2 [145, 181,182,183]

  • Xenografts of foreign tumor cells in the model have shown that the chicken embryo is not able to mount a proper immune response until ED12, though there is a visible infiltration of avian heterophils in the tumor microenvironment [11]

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Summary

INTRODUCTION

The immune system has vital functions for the organism, from defense to homeostasis. Its efficiency is mainly based on a constant balance between activation and tolerance, which helps protect the organism against dangers such as pathogens and abnormal cells, without disturbing its own cells. The avian CAM functions as a homolog of the mammalian placenta, which provides the egg with a rich capillary vascular network and an interface for gas exchange [10, 11] It can be used in biomedical research for a multitude of applications, such as evaluating angiogenesis, tumor growth, metastasis, and therapy responses [12,13,14,15,16,17,18]. This model is far from new: Rous and Murphy initially used it in 1911 to demonstrate the growth of chicken sarcoma tumors transplanted onto the CAM [19, 20]. This review will attempt to describe and explain the various advantages of the chicken embryo model, and its relevancy for immunebased studies

OVERVIEW OF THE MATURE CHICKEN IMMUNE SYSTEM
Morphology of the Lymphoid System
The Diverse Panel of the Avian Immune Cells
Key Receptors and Molecules on Immune Cells
Cytokines and Chemokines
Inflammation
THE CHICKEN EMBRYO AS A NEW PARADIGM FOR IMMUNE-BASED STUDIES
Findings
DISCUSSION
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