Reconciling Mouse and Human Immunology at the Altar of Genetics

Author:

Gros Philippe1,Casanova Jean-Laurent23

Affiliation:

1. McGill University Research Center on Complex Traits, Department of Biochemistry, and Department of Human Genetics, McGill University, Montréal, Québec, Canada;

2. Howard Hughes Medical Institute and St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA;

3. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, and University of Paris Cité, Imagine Institute and Necker Hospital for Sick Children, Paris, France

Abstract

Immunity to infection has been extensively studied in humans and mice bearing naturally occurring or experimentally introduced germline mutations. Mouse studies are sometimes neglected by human immunologists, on the basis that mice are not humans and the infections studied are experimental and not natural. Conversely, human studies are sometimes neglected by mouse immunologists, on the basis of the uncontrolled conditions of study and small numbers of patients. However, both sides would agree that the infectious phenotypes of patients with inborn errors of immunity often differ from those of the corresponding mutant mice. Why is that? We argue that this important question is best addressed by revisiting and reinterpreting the findings of both mouse and human studies from a genetic perspective. Greater caution is required for reverse-genetics studies than for forward-genetics studies, but genetic analysis is sufficiently strong to define the studies likely to stand the test of time. Genetically robust mouse and human studies can provide invaluable complementary insights into the mechanisms of immunity to infection common and specific to these two species.

Publisher

Annual Reviews

Subject

Immunology,Immunology and Allergy

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