Published in:
01-08-2018 | Commentary
A Brief Historical Perspective on the Pathological Consequences of Excessive Type I Interferon Exposure In vivo
Authors:
Yanick J. Crow, Pierre Lebon, Jean-Laurent Casanova, Ion Gresser
Published in:
Journal of Clinical Immunology
|
Issue 6/2018
Login to get access
Excerpt
Interferon was described by Isaacs and Lindenmann in 1957 [
1,
2], and its importance in antiviral host defense was first demonstrated in 1960 [
3]. Virelizier and Gresser were the first to show that endogenous interferon type I mediated one example of genetically determined resistance to a viral infection, when they found that injection of an anti-type I interferon IgG overcame the innate resistance of C3H and A/J mice to mouse hepatitis virus [
4]. These results were then extended by Haller and colleagues, using the same anti-IFN IgG to render a Mendelian-determined resistant strain of mice fully susceptible to the lethal effects of influenza A virus [
5,
6]. Molecular confirmation of these data came through the definition of murine models lacking the type I interferon receptor and relevant downstream signaling molecules [
7‐
9] and the study of human inborn errors of immunity, beginning with the identification of inherited complete STAT1 deficiency in 2003 [
10,
11]. The phenotypes of
Ifnar1,
Ifnar2,
Stat1,
Stat2,
Isg15, and
Irf9-deficient mice and the corresponding human mutant states differ somewhat, in regard to the pattern of expression of interferon stimulated genes and susceptibility to viruses, suggesting that each of these components is essential in its own way for a proper interferon response [
12]. Beyond the more specialized roles of interferon lambda and gamma in epithelial defense and macrophage activation respectively [
13‐
15], definition of specific functions of individual interferon alpha subtypes and interferon beta has remained elusive, although their mere diversity and different patterns of evolutionary selection [
16] suggest discrete and perhaps non-overlapping activities. Overall, 50 years of experimentation has established that type I interferons are globally essential for host defense against a variety of viruses in all species examined. …