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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

Impact of IFNL on Th1/Th2 cytokine profiling. The IFNL3 major allele genotype shows a predominant polarization to a macrophage M1 phenotype, whereas the minor allele genotype may show a relative increase of M2 phenotype. These macrophage phenotypes are associated with the downstream regulation and polarization of Th1 and Th2 cells. NK cells, natural killer cells.
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fig4: Impact of IFNL on Th1/Th2 cytokine profiling. The IFNL3 major allele genotype shows a predominant polarization to a macrophage M1 phenotype, whereas the minor allele genotype may show a relative increase of M2 phenotype. These macrophage phenotypes are associated with the downstream regulation and polarization of Th1 and Th2 cells. NK cells, natural killer cells.

Mentions: Interestingly, the differentiation cascade of monocytes to macrophages is influenced by IFNL.88 IFNL1 increases TLR-induced IL-12p40 production in human monocyte-derived macrophages. Furthermore, IFNL1-treated macrophages were more responsive to IFN-γ, because IFNL1 enhanced IFN-γ-induced IL-12p40 and tumor necrosis factor production by macrophages following R848 stimulation. In addition, IFNL1 upregulated, whereas IFN-α downregulated, the surface expression of the IFN-γ receptor α-subunit on macrophages, which affected the responsiveness of TLR-challenged macrophages to IFN-γ.88 This data highlights the diverse effects of IFN-α and IFNL1 in modulating macrophage populations. The influence of IFNL3/4 SNPs and IL-28RA genotypic background on macrophage polarization and function remains to be studied, but affecting macrophages in general will have a significant impact on host responses to infection (Figure 4).


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)

Impact of IFNL on Th1/Th2 cytokine profiling. The IFNL3 major allele genotype shows a predominant polarization to a macrophage M1 phenotype, whereas the minor allele genotype may show a relative increase of M2 phenotype. These macrophage phenotypes are associated with the downstream regulation and polarization of Th1 and Th2 cells. NK cells, natural killer cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Impact of IFNL on Th1/Th2 cytokine profiling. The IFNL3 major allele genotype shows a predominant polarization to a macrophage M1 phenotype, whereas the minor allele genotype may show a relative increase of M2 phenotype. These macrophage phenotypes are associated with the downstream regulation and polarization of Th1 and Th2 cells. NK cells, natural killer cells.
Mentions: Interestingly, the differentiation cascade of monocytes to macrophages is influenced by IFNL.88 IFNL1 increases TLR-induced IL-12p40 production in human monocyte-derived macrophages. Furthermore, IFNL1-treated macrophages were more responsive to IFN-γ, because IFNL1 enhanced IFN-γ-induced IL-12p40 and tumor necrosis factor production by macrophages following R848 stimulation. In addition, IFNL1 upregulated, whereas IFN-α downregulated, the surface expression of the IFN-γ receptor α-subunit on macrophages, which affected the responsiveness of TLR-challenged macrophages to IFN-γ.88 This data highlights the diverse effects of IFN-α and IFNL1 in modulating macrophage populations. The influence of IFNL3/4 SNPs and IL-28RA genotypic background on macrophage polarization and function remains to be studied, but affecting macrophages in general will have a significant impact on host responses to infection (Figure 4).

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