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The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections.

Egli A, Santer DM, O'Shea D, Tyrrell DL, Houghton M - Emerg Microbes Infect (2014)

Bottom Line: Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection.It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines.In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

View Article: PubMed Central - PubMed

Affiliation: Infection Biology, Department of Biomedicine, University Hospital of Basel , 4031 Basel, Switzerland ; Clinical Microbiology, University Hospital of Basel , 4031 Basel, Switzerland.

ABSTRACT
Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host-pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

No MeSH data available.


Related in: MedlinePlus

Expression dynamics of IFNs and ISGs during viral infection or inflammatory stimulation. Red line represents IFNL3, blue line IFN-α and black line IFNL4 expression dynamics. The lower panel illustrates the amount of ISG expression.
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fig2: Expression dynamics of IFNs and ISGs during viral infection or inflammatory stimulation. Red line represents IFNL3, blue line IFN-α and black line IFNL4 expression dynamics. The lower panel illustrates the amount of ISG expression.

Mentions: IFNL4 mRNA could be detected in primary human hepatocytes (with the required single nucleotide polymorphism (SNP)) 2–4 h after stimulation with poly(I:C) and after in vitro infection with HCV. However, a rapid downregulation of IFNL4 mRNA expression at 8 h was observed. In contrast, IFNL3 mRNA was still expressed 24 h after stimulation (Figure 2).21 The rapid downregulation after stimulation may suggest either a lack of an amplifying positive feedback loop, or rapid induction of a specific negative feedback mechanism. Interestingly, in liver biopsies from non-HCV-infected patients, a baseline mRNA expression of IFNL4 could be observed.21 Although this may suggest that IFNL4 is expressed in conditions unrelated to HCV, activation of this signaling pathway may happen through a wide spectrum of stimuli. DCs have not yet been specifically explored as a source of IFNL4.


The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections.

Egli A, Santer DM, O'Shea D, Tyrrell DL, Houghton M - Emerg Microbes Infect (2014)

Expression dynamics of IFNs and ISGs during viral infection or inflammatory stimulation. Red line represents IFNL3, blue line IFN-α and black line IFNL4 expression dynamics. The lower panel illustrates the amount of ISG expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126180&req=5

fig2: Expression dynamics of IFNs and ISGs during viral infection or inflammatory stimulation. Red line represents IFNL3, blue line IFN-α and black line IFNL4 expression dynamics. The lower panel illustrates the amount of ISG expression.
Mentions: IFNL4 mRNA could be detected in primary human hepatocytes (with the required single nucleotide polymorphism (SNP)) 2–4 h after stimulation with poly(I:C) and after in vitro infection with HCV. However, a rapid downregulation of IFNL4 mRNA expression at 8 h was observed. In contrast, IFNL3 mRNA was still expressed 24 h after stimulation (Figure 2).21 The rapid downregulation after stimulation may suggest either a lack of an amplifying positive feedback loop, or rapid induction of a specific negative feedback mechanism. Interestingly, in liver biopsies from non-HCV-infected patients, a baseline mRNA expression of IFNL4 could be observed.21 Although this may suggest that IFNL4 is expressed in conditions unrelated to HCV, activation of this signaling pathway may happen through a wide spectrum of stimuli. DCs have not yet been specifically explored as a source of IFNL4.

Bottom Line: Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection.It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines.In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

View Article: PubMed Central - PubMed

Affiliation: Infection Biology, Department of Biomedicine, University Hospital of Basel , 4031 Basel, Switzerland ; Clinical Microbiology, University Hospital of Basel , 4031 Basel, Switzerland.

ABSTRACT
Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host-pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

No MeSH data available.


Related in: MedlinePlus