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Disease-promoting effects of type I interferons in viral, bacterial, and coinfections.

Davidson S, Maini MK, Wack A - J. Interferon Cytokine Res. (2015)

Bottom Line: While type I interferons (IFNs) are universally acknowledged for their antiviral and immunostimulatory functions, there is increasing appreciation of the detrimental effects of inappropriate, excessive, or mistimed type I IFN responses in viral and bacterial infections.The underlying mechanisms by which type I IFNs promote susceptibility or severity include direct tissue damage by apoptosis induction or suppression of proliferation in tissue cells, immunopathology due to excessive inflammation, and cell death induced by TRAIL- and Fas-expressing immune cells, as well as immunosuppression through IL-10, IL-27, PD-L1, IL-1Ra, and other regulatory molecules that antagonize the induction or action of IL-1, IL-12, IL-17, IFN-γ, KC, and other effectors of the immune response.This review discusses current understanding of the parameters of signal strength, duration, timing, location, and cellular recipients that determine whether type I IFNs have beneficial or detrimental effects in infection.

View Article: PubMed Central - PubMed

Affiliation: 1 Division of Immunoregulation, MRC National Institute for Medical Research , Mill Hill, London, United Kingdom .

ABSTRACT
While type I interferons (IFNs) are universally acknowledged for their antiviral and immunostimulatory functions, there is increasing appreciation of the detrimental effects of inappropriate, excessive, or mistimed type I IFN responses in viral and bacterial infections. The underlying mechanisms by which type I IFNs promote susceptibility or severity include direct tissue damage by apoptosis induction or suppression of proliferation in tissue cells, immunopathology due to excessive inflammation, and cell death induced by TRAIL- and Fas-expressing immune cells, as well as immunosuppression through IL-10, IL-27, PD-L1, IL-1Ra, and other regulatory molecules that antagonize the induction or action of IL-1, IL-12, IL-17, IFN-γ, KC, and other effectors of the immune response. Bacterial superinfections following influenza infection are a prominent example of a situation where type I IFNs can misdirect the immune response. This review discusses current understanding of the parameters of signal strength, duration, timing, location, and cellular recipients that determine whether type I IFNs have beneficial or detrimental effects in infection.

No MeSH data available.


Related in: MedlinePlus

Partial redundancy of types I and III IFNs in infection by influenza and other respiratory viruses. Both IFN-αβ and IFN-λ are induced upon influenza infection. Their effects depend on the distribution of their receptors: Epithelial cells express receptors for both IFN types, and both these IFNs can mediate the induction of the epithelial antiviral response (left). Immune cells express only IFN-αβ receptors and can be stimulated or inhibited by type I IFN (right). STAT1/2 is involved in signal transduction downstream of both type I and type III receptors. The degree and nature of immune activation determines whether the net result of all combined type I IFN-mediated effects is protective or pathogenic.
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f3: Partial redundancy of types I and III IFNs in infection by influenza and other respiratory viruses. Both IFN-αβ and IFN-λ are induced upon influenza infection. Their effects depend on the distribution of their receptors: Epithelial cells express receptors for both IFN types, and both these IFNs can mediate the induction of the epithelial antiviral response (left). Immune cells express only IFN-αβ receptors and can be stimulated or inhibited by type I IFN (right). STAT1/2 is involved in signal transduction downstream of both type I and type III receptors. The degree and nature of immune activation determines whether the net result of all combined type I IFN-mediated effects is protective or pathogenic.

Mentions: Why IFN-λ is protective in some viral infections and not all comes down to virus tissue tropism. Unlike the hepatotropic viruses (Thogotovirus and Lassa fever virus) or indeed other viruses such as LCMV and VSV, which can infect a variety of cell types, influenza, RSV, and HMPV replication are restricted to epithelial cells of the lung (Schickli and others 2005; Collins and Graham 2008; Crotta and others 2013). Thus, type III and type I IFNs are able to act redundantly and restrict spread of viruses whose replication is restricted to cell types, which express both IFN-αβR and IFN-λR, essentially cells at mucosal surfaces (Fig. 3). In contrast, for viruses that can infect cell types not responsive to IFN-λ signaling, including immune cells, neurons, and murine hepatic cells, IFN-λ is not sufficient to protect against virus dissemination.


Disease-promoting effects of type I interferons in viral, bacterial, and coinfections.

Davidson S, Maini MK, Wack A - J. Interferon Cytokine Res. (2015)

Partial redundancy of types I and III IFNs in infection by influenza and other respiratory viruses. Both IFN-αβ and IFN-λ are induced upon influenza infection. Their effects depend on the distribution of their receptors: Epithelial cells express receptors for both IFN types, and both these IFNs can mediate the induction of the epithelial antiviral response (left). Immune cells express only IFN-αβ receptors and can be stimulated or inhibited by type I IFN (right). STAT1/2 is involved in signal transduction downstream of both type I and type III receptors. The degree and nature of immune activation determines whether the net result of all combined type I IFN-mediated effects is protective or pathogenic.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4389918&req=5

f3: Partial redundancy of types I and III IFNs in infection by influenza and other respiratory viruses. Both IFN-αβ and IFN-λ are induced upon influenza infection. Their effects depend on the distribution of their receptors: Epithelial cells express receptors for both IFN types, and both these IFNs can mediate the induction of the epithelial antiviral response (left). Immune cells express only IFN-αβ receptors and can be stimulated or inhibited by type I IFN (right). STAT1/2 is involved in signal transduction downstream of both type I and type III receptors. The degree and nature of immune activation determines whether the net result of all combined type I IFN-mediated effects is protective or pathogenic.
Mentions: Why IFN-λ is protective in some viral infections and not all comes down to virus tissue tropism. Unlike the hepatotropic viruses (Thogotovirus and Lassa fever virus) or indeed other viruses such as LCMV and VSV, which can infect a variety of cell types, influenza, RSV, and HMPV replication are restricted to epithelial cells of the lung (Schickli and others 2005; Collins and Graham 2008; Crotta and others 2013). Thus, type III and type I IFNs are able to act redundantly and restrict spread of viruses whose replication is restricted to cell types, which express both IFN-αβR and IFN-λR, essentially cells at mucosal surfaces (Fig. 3). In contrast, for viruses that can infect cell types not responsive to IFN-λ signaling, including immune cells, neurons, and murine hepatic cells, IFN-λ is not sufficient to protect against virus dissemination.

Bottom Line: While type I interferons (IFNs) are universally acknowledged for their antiviral and immunostimulatory functions, there is increasing appreciation of the detrimental effects of inappropriate, excessive, or mistimed type I IFN responses in viral and bacterial infections.The underlying mechanisms by which type I IFNs promote susceptibility or severity include direct tissue damage by apoptosis induction or suppression of proliferation in tissue cells, immunopathology due to excessive inflammation, and cell death induced by TRAIL- and Fas-expressing immune cells, as well as immunosuppression through IL-10, IL-27, PD-L1, IL-1Ra, and other regulatory molecules that antagonize the induction or action of IL-1, IL-12, IL-17, IFN-γ, KC, and other effectors of the immune response.This review discusses current understanding of the parameters of signal strength, duration, timing, location, and cellular recipients that determine whether type I IFNs have beneficial or detrimental effects in infection.

View Article: PubMed Central - PubMed

Affiliation: 1 Division of Immunoregulation, MRC National Institute for Medical Research , Mill Hill, London, United Kingdom .

ABSTRACT
While type I interferons (IFNs) are universally acknowledged for their antiviral and immunostimulatory functions, there is increasing appreciation of the detrimental effects of inappropriate, excessive, or mistimed type I IFN responses in viral and bacterial infections. The underlying mechanisms by which type I IFNs promote susceptibility or severity include direct tissue damage by apoptosis induction or suppression of proliferation in tissue cells, immunopathology due to excessive inflammation, and cell death induced by TRAIL- and Fas-expressing immune cells, as well as immunosuppression through IL-10, IL-27, PD-L1, IL-1Ra, and other regulatory molecules that antagonize the induction or action of IL-1, IL-12, IL-17, IFN-γ, KC, and other effectors of the immune response. Bacterial superinfections following influenza infection are a prominent example of a situation where type I IFNs can misdirect the immune response. This review discusses current understanding of the parameters of signal strength, duration, timing, location, and cellular recipients that determine whether type I IFNs have beneficial or detrimental effects in infection.

No MeSH data available.


Related in: MedlinePlus