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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

Multiple effects of IFN-αβ on immune and epithelial cells that can contribute to disease in specific infections. Only direct enhancing (green) and inhibitory (red) effects by IFN-αβ are color coded, secondary effects are in black. IFN-αβ can enhance production of IL-10, proinflammatory cytokines, and IL-27 and can block directly or indirectly the cytokines, IL-1, IL-12, IL-17, IFN-γ, and KC. Detrimental effects can be due to the suppression of antibacterial responses (IL-1, IL-17, IFN-γ, and KC) or to overstimulation of inflammation leading to damage by apoptosis of tissue cells or immune suppression by apoptosis of immune cells.
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f1: Multiple effects of IFN-αβ on immune and epithelial cells that can contribute to disease in specific infections. Only direct enhancing (green) and inhibitory (red) effects by IFN-αβ are color coded, secondary effects are in black. IFN-αβ can enhance production of IL-10, proinflammatory cytokines, and IL-27 and can block directly or indirectly the cytokines, IL-1, IL-12, IL-17, IFN-γ, and KC. Detrimental effects can be due to the suppression of antibacterial responses (IL-1, IL-17, IFN-γ, and KC) or to overstimulation of inflammation leading to damage by apoptosis of tissue cells or immune suppression by apoptosis of immune cells.

Mentions: The prototype antiviral cytokine family, type I interferons (IFNs), inhibits replication and spread of a range of viruses both in vivo and in vitro (Isaacs and Lindenmann 1957; Muller and others 1994; Schneider and others 2014). In addition, type I IFNs can signal to almost every cell type in the body, including immune cells, and thus are potent immunomodulators, ensuring a timely and robust immune response to an invading pathogen. The pluripotency of type I IFNs allows for interaction with the immune system, promoting secretion of specific cytokines such as IL-10 and IL-6 and blocking production or function of others, for example, IL-17, IL-1, and IFN-γ (Fig. 1). Yet, within these extensive and strong effects on the immune response also lies the potential for pathogenesis (Trinchieri 2010).


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

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

Multiple effects of IFN-αβ on immune and epithelial cells that can contribute to disease in specific infections. Only direct enhancing (green) and inhibitory (red) effects by IFN-αβ are color coded, secondary effects are in black. IFN-αβ can enhance production of IL-10, proinflammatory cytokines, and IL-27 and can block directly or indirectly the cytokines, IL-1, IL-12, IL-17, IFN-γ, and KC. Detrimental effects can be due to the suppression of antibacterial responses (IL-1, IL-17, IFN-γ, and KC) or to overstimulation of inflammation leading to damage by apoptosis of tissue cells or immune suppression by apoptosis of immune cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Multiple effects of IFN-αβ on immune and epithelial cells that can contribute to disease in specific infections. Only direct enhancing (green) and inhibitory (red) effects by IFN-αβ are color coded, secondary effects are in black. IFN-αβ can enhance production of IL-10, proinflammatory cytokines, and IL-27 and can block directly or indirectly the cytokines, IL-1, IL-12, IL-17, IFN-γ, and KC. Detrimental effects can be due to the suppression of antibacterial responses (IL-1, IL-17, IFN-γ, and KC) or to overstimulation of inflammation leading to damage by apoptosis of tissue cells or immune suppression by apoptosis of immune cells.
Mentions: The prototype antiviral cytokine family, type I interferons (IFNs), inhibits replication and spread of a range of viruses both in vivo and in vitro (Isaacs and Lindenmann 1957; Muller and others 1994; Schneider and others 2014). In addition, type I IFNs can signal to almost every cell type in the body, including immune cells, and thus are potent immunomodulators, ensuring a timely and robust immune response to an invading pathogen. The pluripotency of type I IFNs allows for interaction with the immune system, promoting secretion of specific cytokines such as IL-10 and IL-6 and blocking production or function of others, for example, IL-17, IL-1, and IFN-γ (Fig. 1). Yet, within these extensive and strong effects on the immune response also lies the potential for pathogenesis (Trinchieri 2010).

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