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Review
. 2018 Sep 11:9:2061.
doi: 10.3389/fimmu.2018.02061. eCollection 2018.

The Dual Nature of Type I and Type II Interferons

Amanda J Lee  1 , Ali A Ashkar  1
Affiliations
Review

The Dual Nature of Type I and Type II Interferons

Amanda J Lee et al. Front Immunol. .

Abstract

Type I and type II interferons (IFN) are central to both combating virus infection and modulating the antiviral immune response. Indeed, an absence of either the receptor for type I IFNs or IFN-y have resulted in increased susceptibility to virus infection, including increased virus replication and reduced survival. However, an emerging area of research has shown that there is a dual nature to these cytokines. Recent evidence has demonstrated that both type I and type II IFNs have immunoregulatory functions during infection and type II immune responses. In this review, we address the dual nature of type I and type II interferons and present evidence that both antiviral and immunomodulatory functions are critical during virus infection to not only limit virus replication and initiate an appropriate antiviral immune response, but to also negatively regulate this response to minimize tissue damage. Both the activating and negatively regulatory properties of type I and II IFNs work in concert with each other to create a balanced immune response that combats the infection while minimizing collateral damage.

Keywords: immunoregulation; innate immunity; interferon-γ; type I interferon; virus infection.

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Figures

Figure 1
Figure 1
The role of IFNs in the innate immune response to HSV-2 infection. (1) IFN-β is produced at 12 h post-infection and through autocrine and paracrine signaling places surrounding cells into an antiviral state. (2) The IFN-β produced at 12 h post-infection also increases production of CCL2 between days 1 and 2 post-infection, which results in inflammatory monocyte recruitment and has been implicated in NK cell recruitment. (3) The recruited inflammatory monocytes result in release of IL-18, which stimulates NK cells to produce IFN-γ at 48 h post-infection. (4) A second wave of type I IFNs, including both IFN-α and IFN-β, are detected at 48 h post-infection. (5) Both IFN-γ and the type I IFNs produced at 48 h post-infection enhance APC antigen presentation capacities to stimulate a Th1 adaptive immune response. (6) Simultaneously, the type I IFNs at 48 h inhibit ILC2-mediated virus-induced immunopathology. IFN-γ, supporting the negative regulatory effects of type I IFN, also suppresses ILC2-mediated immunopathology.
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