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  • Review Article
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Studying immunity to zoonotic diseases in the natural host — keeping it real

Nature Reviews Immunology volume 13, pages 851–861 (2013)Cite this article

Subjects

Key Points

  • Zoonotic viruses pose a serious threat to human and animal health. Studying the immune response to zoonotic pathogens in the natural reservoir hosts, rather than traditional animal models, offers important insights into control strategies.

  • Comparative studies in natural host systems have provided key information and improved our understanding of co-evolution of hosts and pathogens. This could lead to the discovery of novel immune mechanisms that control viral replication.

  • Understanding the differences between the immune systems of domesticated and wild animal hosts and comparing them to the human immune system is crucial for unravelling the complex disease mechanisms involved in zoonotic infections and for developing new strategies for disrupting their transmission to humans.

  • The use of non-traditional animal models for research poses many challenges. These include the need for specialist high-biosecurity containment facilities, a lack of species-specific reagents for immunology studies, and complex husbandry, ethics and welfare issues.

  • Whole-genome sequencing and comparative analysis of host species have provided key insights into how different immune responses are made to the same pathogen.

  • The identification of key differences in immune pathways between susceptible and non-susceptible hosts might offer clues for developing disease intervention strategies, including new antiviral vaccines and therapies, and disease-resistant animals.

Abstract

Zoonotic viruses that emerge from wildlife and domesticated animals pose a serious threat to human and animal health. In many instances, mouse models have improved our understanding of the human immune response to infection; however, when dealing with emerging zoonotic diseases, they may be of limited use. This is particularly the case when the model fails to reproduce the disease status that is seen in the natural reservoir, transmission species or human host. In this Review, we discuss how researchers are placing more emphasis on the study of the immune response to zoonotic infections in the natural reservoir hosts and spillover species. Such studies will not only lead to a greater understanding of how these infections induce variable disease and immune responses in distinct species but also offer important insights into the evolution of mammalian immune systems.

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Figure 1: Emergence of zoonoses.
Figure 2: The severity of emerging infectious diseases is influenced by the host–pathogen interaction.
Figure 3: The host immune response to an infection influences the disease outcome.
Figure 4: Positive selection of bat genes.

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Authors and Affiliations

  1. CSIRO Biosecurity Flagship, Australian Animal Health Laboratory, Geelong, 3220, Victoria, Australia

    Andrew G. D. Bean, Michelle L. Baker, Cameron R. Stewart, Christopher Cowled, Celine Deffrasnes, Lin-Fa Wang & John W. Lowenthal

  2. Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, 169857, Singapore

    Lin-Fa Wang

  3. School of Medicine, Deakin University, Waurn Ponds, 3216, Victoria, Australia

    John W. Lowenthal

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Correspondence to John W. Lowenthal.

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Supplementary information

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Natural reservoir hosts and susceptible hosts involved in transmission of bacterial, prion, parasitic and other viral zoonotic diseases (PDF 167 kb)

Glossary

Variable lymphocyte receptors

Alternative forms of somatically diversified antigen receptors expressed by lymphocytes of jawless vertebrates. The combinatorial diversity of these receptors is based on variable numbers of leucine-rich repeat elements assembled by a gene-conversion process.

Bursa of Fabricius

A primary lymphoid organ that is only found in birds. B cells mature in this organ, and indeed were first observed and named after this site: the 'B' in B cell refers to 'bursa-derived'.

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Bean, A., Baker, M., Stewart, C. et al. Studying immunity to zoonotic diseases in the natural host — keeping it real. Nat Rev Immunol 13, 851–861 (2013). https://doi.org/10.1038/nri3551

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