Interferon Lambda Genetics and Biology in Regulation of Viral Control

Emily A Hemann, Michael Gale Jr, Ram Savan, Emily A Hemann, Michael Gale Jr, Ram Savan

Abstract

Type III interferons, also known as interferon lambdas (IFNλs), are the most recent addition to the IFN family following their discovery in 2003. Initially, IFNλ was demonstrated to induce expression of interferon-stimulated genes and exert antiviral properties in a similar manner to type I IFNs. However, while IFNλ has been described to have largely overlapping expression and function with type I IFNs, it has become increasingly clear that type III IFNs also have distinct functions from type I IFNs. In contrast to type I IFNs, whose receptor is ubiquitously expressed, type III IFNs signal and function largely at barrier epithelial surfaces, such as the respiratory and gastrointestinal tracts, as well as the blood-brain barrier. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have also been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. In this review, we discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections.

Keywords: immune cells; immunity; infectious disease; interferon; interferon lambda; virus.

Figures

Figure 1
Figure 1
General induction and receptor signaling pathways of type I and type III IFNs. Recognition of virus by multiple pattern recognition receptor pathways leads to the activation of the transcription factors IRF1, IRF3, IRF7, and NF-κB to induce transcription, translation, and secretion of type I IFN (IFNα and IFNβ) and type III IFN [interferon lambda (IFNλ)]. Type I and type III IFNs signal to surrounding cells via distinct receptors to induce activation of the JAK–STAT pathway leading to the production of IFN-stimulated genes (ISGs) that can amplify the IFN signal and induce an antiviral state in infected cells/tissues.
Figure 2
Figure 2
Interferon lambda (IFNλ) and IFNα/β differentially modulate immune responses during acute viral infection and tissue inflammation. (A) Following viral infection/tissue inflammation, IFNλ modulates functions of dendritic cells (DCs) neutrophils, CD4 T cells, and the B-cell antibody response. IFNλ signaling may also regulate macrophage, NK cell, and CD8 T cell function during infection/tissue inflammation (B) type I IFN (IFNα and IFNβ) have been the subject of a greater number of studies and have more defined roles during virus infection and tissue inflammation. Type I IFN enhances functions of DCs, macrophages, NK cells, B cells, CD4 T cells, and CD8 T cells toward an inflammatory/antiviral state.

References

    1. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol (2014) 14(1):36–49.10.1038/nri3581
    1. McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I interferons in infectious disease. Nat Rev Immunol (2015) 15(2):87–103.10.1038/nri3787
    1. Chow KT, Gale M, Jr. SnapShot: interferon signaling. Cell (2015) 163(7):1808–1808.e1.10.1016/j.cell.2015.12.008
    1. Secombes CJ, Zou J. Evolution of interferons and interferon receptors. Front Immunol (2017) 8:209.10.3389/fimmu.2017.00209
    1. Boudinot P, Langevin C, Secombes CJ, Levraud JP. The peculiar characteristics of fish type I interferons. Viruses (2016) 8(11):1–17.10.3390/v8110298
    1. Sang Y, Liu Q, Lee J, Ma W, McVey DS, Blecha F. Expansion of amphibian intronless interferons revises the paradigm for interferon evolution and functional diversity. Sci Rep (2016) 6:29072.10.1038/srep29072
    1. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol (2003) 4(1):69–77.10.1038/ni875
    1. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol (2003) 4(1):63–8.10.1038/ni873
    1. Chen SN, Zhang XW, Li L, Ruan BY, Huang B, Huang WS, et al. Evolution of IFN-lambda in tetrapod vertebrates and its functional characterization in green anole lizard (Anolis carolinensis). Dev Comp Immunol (2016) 61:208–24.10.1016/j.dci.2016.04.004
    1. Gad HH, Dellgren C, Hamming OJ, Vends S, Paludan SR, Hartmann R. Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family. J Biol Chem (2009) 284(31):20869–75.10.1074/jbc.M109.002923
    1. Manry J, Laval G, Patin E, Fornarino S, Itan Y, Fumagalli M, et al. Evolutionary genetic dissection of human interferons. J Exp Med (2011) 208(13):2747–59.10.1084/jem.20111680
    1. Hoffmann HH, Schneider WM, Rice CM. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol (2015) 36(3):124–38.10.1016/j.it.2015.01.004
    1. Lasfar A, Lewis-Antes A, Smirnov SV, Anantha S, Abushahba W, Tian B, et al. Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Res (2006) 66(8):4468–77.10.1158/0008-5472.CAN-05-3653
    1. Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C, et al. IL-28A (IFN-lambda2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med (2011) 3(6):348–61.10.1002/emmm.201100142
    1. Egli A, Santer DM, O’Shea D, Barakat K, Syedbasha M, Vollmer M, et al. IL-28B is a key regulator of B- and T-cell vaccine responses against influenza. PLoS Pathog (2014) 10(12):e1004556.10.1371/journal.ppat.1004556
    1. Wei H, Wang S, Chen Q, Chen Y, Chi X, Zhang L, et al. Suppression of interferon lambda signaling by SOCS-1 results in their excessive production during influenza virus infection. PLoS Pathog (2014) 10(1):e1003845.10.1371/journal.ppat.1003845
    1. Lazear HM, Nice TJ, Diamond MS. Interferon-lambda: immune functions at barrier surfaces and beyond. Immunity (2015) 43(1):15–28.10.1016/j.immuni.2015.07.001
    1. Iversen MB, Paludan SR. Mechanisms of type III interferon expression. J Interferon Cytokine Res (2010) 30(8):573–8.10.1089/jir.2010.0063
    1. Levy DE, Marie IJ, Durbin JE. Induction and function of type I and III interferon in response to viral infection. Curr Opin Virol (2011) 1(6):476–86.10.1016/j.coviro.2011.11.001
    1. Durbin RK, Kotenko SV, Durbin JE. Interferon induction and function at the mucosal surface. Immunol Rev (2013) 255(1):25–39.10.1111/imr.12101
    1. Odendall C, Dixit E, Stavru F, Bierne H, Franz KM, Durbin AF, et al. Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nat Immunol (2014) 15(8):717–26.10.1038/ni.2915
    1. Coccia EM, Severa M, Giacomini E, Monneron D, Remoli ME, Julkunen I, et al. Viral infection and toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells. Eur J Immunol (2004) 34(3):796–805.10.1002/eji.200324610
    1. Siren J, Pirhonen J, Julkunen I, Matikainen S. IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29. J Immunol (2005) 174(4):1932–7.10.4049/jimmunol.174.4.1932
    1. Zhang X, Brann TW, Zhou M, Yang J, Oguariri RM, Lidie KB, et al. Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN. J Immunol (2011) 186(8):4541–5.10.4049/jimmunol.1003389
    1. Sui H, Zhou M, Imamichi H, Jiao X, Sherman BT, Lane HC, et al. STING is an essential mediator of the Ku70-mediated production of IFN-lambda1 in response to exogenous DNA. Sci Signal (2017) 10(488): eaah5054.10.1126/scisignal.aah5054
    1. Bolen CR, Ding S, Robek MD, Kleinstein SH. Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression. Hepatology (2014) 59(4):1262–72.10.1002/hep.26657
    1. Lin JD, Feng N, Sen A, Balan M, Tseng HC, McElrath C, et al. Distinct roles of type I and type III interferons in intestinal immunity to homologous and heterologous rotavirus infections. PLoS Pathog (2016) 12(4):e1005600.10.1371/journal.ppat.1005600
    1. Osterlund PI, Pietila TE, Veckman V, Kotenko SV, Julkunen I. IFN regulatory factor family members differentially regulate the expression of type III IFN (IFN-lambda) genes. J Immunol (2007) 179(6):3434–42.10.4049/jimmunol.179.6.3434
    1. Thomson SJ, Goh FG, Banks H, Krausgruber T, Kotenko SV, Foxwell BM, et al. The role of transposable elements in the regulation of IFN-lambda1 gene expression. Proc Natl Acad Sci U S A (2009) 106(28):11564–9.10.1073/pnas.0904477106
    1. Pott J, Mahlakoiv T, Mordstein M, Duerr CU, Michiels T, Stockinger S, et al. IFN-lambda determines the intestinal epithelial antiviral host defense. Proc Natl Acad Sci U S A (2011) 108(19):7944–9.10.1073/pnas.1100552108
    1. Jewell NA, Cline T, Mertz SE, Smirnov SV, Flano E, Schindler C, et al. Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. J Virol (2010) 84(21):11515–22.10.1128/JVI.01703-09
    1. Robek MD, Boyd BS, Chisari FV. Lambda interferon inhibits hepatitis B and C virus replication. J Virol (2005) 79(6):3851–4.10.1128/JVI.79.6.3851-3854.2005
    1. Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR. Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol (2006) 80(9):4501–9.10.1128/JVI.80.9.4501-4509.2006
    1. Baldridge MT, Lee S, Brown JJ, McAllister N, Urbanek K, Dermody TS, et al. Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of interferon lambda against norovirus and reovirus. J Virol (2017) 91(7): e02079–16.10.1128/JVI.02079-16
    1. Galani IE, Triantafyllia V, Eleminiadou EE, Koltsida O, Stavropoulos A, Manioudaki M, et al. Interferon-lambda mediates non-redundant front-line antiviral protection against influenza virus infection without compromising host fitness. Immunity (2017) 46(5):875–90.e6.10.1016/j.immuni.2017.04.025
    1. Kotenko SV. IFN-lambdas. Curr Opin Immunol (2011) 23(5):583–90.10.1016/j.coi.2011.07.007
    1. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev (2008) 226:205–18.10.1111/j.1600-065X.2008.00706.x
    1. Lee S, Baldridge MT. Interferon-lambda: a potent regulator of intestinal viral infections. Front Immunol (2017) 8:749.10.3389/fimmu.2017.00749
    1. Piganis RA, De Weerd NA, Gould JA, Schindler CW, Mansell A, Nicholson SE, et al. Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon alpha receptor (IFNAR1)-associated tyrosine kinase Tyk2. J Biol Chem (2011) 286(39):33811–8.10.1074/jbc.M111.270207
    1. Liu B, Chen S, Guan Y, Chen L. Type III interferon induces distinct SOCS1 expression pattern that contributes to delayed but prolonged activation of Jak/STAT signaling pathway: implications for treatment non-response in HCV patients. PLoS One (2015) 10(7):e0133800.10.1371/journal.pone.0133800
    1. Blumer T, Coto-Llerena M, Duong FHT, Heim MH. SOCS1 is an inducible negative regulator of IFN lambda induced gene expression in vivo. J Biol Chem (2017) 292:17928–38.10.1074/jbc.M117.788877
    1. Mendoza JL, Schneider WM, Hoffmann HH, Vercauteren K, Jude KM, Xiong A, et al. The IFN-lambda-IFN-lambdaR1-IL-10Rbeta complex reveals structural features underlying type III IFN functional plasticity. Immunity (2017) 46(3):379–92.10.1016/j.immuni.2017.02.017
    1. Witte K, Gruetz G, Volk HD, Looman AC, Asadullah K, Sterry W, et al. Despite IFN-lambda receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines. Genes Immun (2009) 10(8):702–14.10.1038/gene.2009.72
    1. Donnelly RP, Kotenko SV. Interferon-lambda: a new addition to an old family. J Interferon Cytokine Res (2010) 30(8):555–64.10.1089/jir.2010.0078
    1. Odendall C, Kagan JC. The unique regulation and functions of type III interferons in antiviral immunity. Curr Opin Virol (2015) 12:47–52.10.1016/j.coviro.2015.02.003
    1. Wack A, Terczynska-Dyla E, Hartmann R. Guarding the frontiers: the biology of type III interferons. Nat Immunol (2015) 16(8):802–9.10.1038/ni.3212
    1. Syedbasha M, Egli A. Interferon lambda: modulating immunity in infectious diseases. Front Immunol (2017) 8:119.10.3389/fimmu.2017.00119
    1. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR, Klucher K, et al. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog (2008) 4(9):e1000151.10.1371/journal.ppat.1000151
    1. Mordstein M, Neugebauer E, Ditt V, Jessen B, Rieger T, Falcone V, et al. Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. J Virol (2010) 84(11):5670–7.10.1128/JVI.00272-10
    1. Nice TJ, Baldridge MT, McCune BT, Norman JM, Lazear HM, Artyomov M, et al. Interferon-lambda cures persistent murine norovirus infection in the absence of adaptive immunity. Science (2015) 347(6219):269–73.10.1126/science.1258100
    1. Parker BS, Rautela J, Hertzog PJ. Antitumour actions of interferons: implications for cancer therapy. Nat Rev Cancer (2016) 16(3):131–44.10.1038/nrc.2016.14
    1. Crotta S, Davidson S, Mahlakoiv T, Desmet CJ, Buckwalter MR, Albert ML, et al. Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia. PLoS Pathog (2013) 9(11):e1003773.10.1371/journal.ppat.1003773
    1. Muir AJ, Arora S, Everson G, Flisiak R, George J, Ghalib R, et al. A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection. J Hepatol (2014) 61(6):1238–46.10.1016/j.jhep.2014.07.022
    1. Davidson S, McCabe TM, Crotta S, Gad HH, Hessel EM, Beinke S, et al. IFNlambda is a potent anti-influenza therapeutic without the inflammatory side effects of IFNalpha treatment. EMBO Mol Med (2016) 8(9):1099–112.10.15252/emmm.201606413
    1. Kim S, Kim MJ, Kim CH, Kang JW, Shin HK, Kim DY, et al. The superiority of IFN-lambda as a therapeutic candidate to control acute influenza viral lung infection. Am J Respir Cell Mol Biol (2017) 56(2):202–12.10.1165/rcmb.2016-0174OC
    1. D’Ambrosio R, Degasperi E, Colombo M, Aghemo A. Direct-acting antivirals: the endgame for hepatitis C? Curr Opin Virol (2017) 24:31–7.10.1016/j.coviro.2017.03.017
    1. Banos-Lara Mdel R, Harvey L, Mendoza A, Simms D, Chouljenko VN, Wakamatsu N, et al. Impact and regulation of lambda interferon response in human metapneumovirus infection. J Virol (2015) 89(1):730–42.10.1128/JVI.02897-14
    1. Hastings AK, Erickson JJ, Schuster JE, Boyd KL, Tollefson SJ, Johnson M, et al. Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. J Virol (2015) 89(8):4405–20.10.1128/JVI.03275-14
    1. Lukacikova L, Oveckova I, Betakova T, Laposova K, Polcicova K, Pastorekova S, et al. Antiviral effect of interferon lambda against lymphocytic choriomeningitis virus. J Interferon Cytokine Res (2015) 35(7):540–53.10.1089/jir.2014.0083
    1. Ank N, Iversen MB, Bartholdy C, Staeheli P, Hartmann R, Jensen UB, et al. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity. J Immunol (2008) 180(4):2474–85.10.4049/jimmunol.180.4.2474
    1. Misumi I, Whitmire JK. IFN-lambda exerts opposing effects on T cell responses depending on the chronicity of the virus infection. J Immunol (2014) 192(8):3596–606.10.4049/jimmunol.1301705
    1. Teijaro JR, Ng C, Lee AM, Sullivan BM, Sheehan KC, Welch M, et al. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science (2013) 340(6129):207–11.10.1126/science.1235214
    1. Wilson EB, Yamada DH, Elsaesser H, Herskovitz J, Deng J, Cheng G, et al. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science (2013) 340(6129):202–7.10.1126/science.1235208
    1. Hsu YL, Wang MY, Ho LJ, Lai JH. Dengue virus infection induces interferon-lambda1 to facilitate cell migration. Sci Rep (2016) 6:24530.10.1038/srep24530
    1. Palma-Ocampo HK, Flores-Alonso JC, Vallejo-Ruiz V, Reyes-Leyva J, Flores-Mendoza L, Herrera-Camacho I, et al. Interferon lambda inhibits dengue virus replication in epithelial cells. Virol J (2015) 12:150.10.1186/s12985-015-0383-4
    1. Orozco S, Schmid MA, Parameswaran P, Lachica R, Henn MR, Beatty R, et al. Characterization of a model of lethal dengue virus 2 infection in C57BL/6 mice deficient in the alpha/beta interferon receptor. J Gen Virol (2012) 93(Pt 10):2152–7.10.1099/vir.0.045088-0
    1. Zust R, Toh YX, Valdes I, Cerny D, Heinrich J, Hermida L, et al. Type I interferon signals in macrophages and dendritic cells control dengue virus infection: implications for a new mouse model to test dengue vaccines. J Virol (2014) 88(13):7276–85.10.1128/JVI.03827-13
    1. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature (2009) 461(7262):399–401.10.1038/nature08309
    1. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet (2009) 41(10):1100–4.10.1038/ng.447
    1. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet (2009) 41(10):1105–9.10.1038/ng.449
    1. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature (2009) 461(7265):798–801.10.1038/nature08463
    1. Sheahan T, Imanaka N, Marukian S, Dorner M, Liu P, Ploss A, et al. Interferon lambda alleles predict innate antiviral immune responses and hepatitis C virus permissiveness. Cell Host Microbe (2014) 15(2):190–202.10.1016/j.chom.2014.01.007
    1. Liu MQ, Zhou DJ, Wang X, Zhou W, Ye L, Li JL, et al. IFN-lambda3 inhibits HIV infection of macrophages through the JAK-STAT pathway. PLoS One (2012) 7(4):e35902.10.1371/journal.pone.0035902
    1. Wang Y, Li J, Wang X, Zhou Y, Zhang T, Ho W. Comparison of antiviral activity of lambda-interferons against HIV replication in macrophages. J Interferon Cytokine Res (2015) 35(3):213–21.10.1089/jir.2014.0064
    1. Tian RR, Guo HX, Wei JF, Yang CK, He SH, Wang JH. IFN-lambda inhibits HIV-1 integration and post-transcriptional events in vitro, but there is only limited in vivo repression of viral production. Antiviral Res (2012) 95(1):57–65.10.1016/j.antiviral.2012.04.011
    1. Lavender KJ, Gibbert K, Peterson KE, Van Dis E, Francois S, Woods T, et al. Interferon alpha subtype-specific suppression of HIV-1 infection in vivo. J Virol (2016) 90(13):6001–13.10.1128/JVI.00451-16
    1. Harris LD, Tabb B, Sodora DL, Paiardini M, Klatt NR, Douek DC, et al. Downregulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques. J Virol (2010) 84(15):7886–91.10.1128/JVI.02612-09
    1. Hardy GA, Sieg S, Rodriguez B, Anthony D, Asaad R, Jiang W, et al. Interferon-alpha is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers. PLoS One (2013) 8(2):e56527.10.1371/journal.pone.0056527
    1. Baldridge MT, Nice TJ, McCune BT, Yokoyama CC, Kambal A, Wheadon M, et al. Commensal microbes and interferon-lambda determine persistence of enteric murine norovirus infection. Science (2015) 347(6219):266–9.10.1126/science.1258025
    1. Nice TJ, Osborne LC, Tomov VT, Artis D, Wherry EJ, Virgin HW. Type I interferon receptor deficiency in dendritic cells facilitates systemic murine norovirus persistence despite enhanced adaptive immunity. PLoS Pathog (2016) 12(6):e1005684.10.1371/journal.ppat.1005684
    1. Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med (2006) 12(9):1023–6.10.1038/nm1462
    1. Foxman EF, Storer JA, Fitzgerald ME, Wasik BR, Hou L, Zhao H, et al. Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proc Natl Acad Sci U S A (2015) 112(3):827–32.10.1073/pnas.1411030112
    1. Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe (2016) 19(2):181–93.10.1016/j.chom.2016.01.007
    1. Lazear HM, Daniels BP, Pinto AK, Huang AC, Vick SC, Doyle SE, et al. Interferon-lambda restricts West Nile virus neuroinvasion by tightening the blood-brain barrier. Sci Transl Med (2015) 7(284):284ra259.10.1126/scitranslmed.aaa4304
    1. Samuel MA, Diamond MS. Alpha/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival. J Virol (2005) 79(21):13350–61.10.1128/JVI.79.21.13350-13361.2005
    1. Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques ET, Jr, et al. Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe (2016) 19(5):705–12.10.1016/j.chom.2016.03.008
    1. Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ, et al. A mouse model of Zika virus pathogenesis. Cell Host Microbe (2016) 19(5):720–30.10.1016/j.chom.2016.03.010
    1. Bowen JR, Quicke KM, Maddur MS, O’Neal JT, McDonald CE, Fedorova NB, et al. Zika virus antagonizes type I interferon responses during infection of human dendritic cells. PLoS Pathog (2017) 13(2):e1006164.10.1371/journal.ppat.1006164
    1. Mahlakoiv T, Hernandez P, Gronke K, Diefenbach A, Staeheli P. Leukocyte-derived IFN-alpha/beta and epithelial IFN-lambda constitute a compartmentalized mucosal defense system that restricts enteric virus infections. PLoS Pathog (2015) 11(4):e1004782.10.1371/journal.ppat.1004782
    1. Dionne KR, Galvin JM, Schittone SA, Clarke P, Tyler KL. Type I interferon signaling limits reoviral tropism within the brain and prevents lethal systemic infection. J Neurovirol (2011) 17(4):314–26.10.1007/s13365-011-0038-1
    1. Hernandez PP, Mahlakoiv T, Yang I, Schwierzeck V, Nguyen N, Guendel F, et al. Interferon-lambda and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection. Nat Immunol (2015) 16(7):698–707.10.1038/ni.3180
    1. Egli A, Levin A, Santer DM, Joyce M, O’Shea D, Thomas BS, et al. Immunomodulatory function of interleukin 28B during primary infection with cytomegalovirus. J Infect Dis (2014) 210(5):717–27.10.1093/infdis/jiu144
    1. Holzki JK, Dag F, Dekhtiarenko I, Rand U, Casalegno-Garduno R, Trittel S, et al. Type I interferon released by myeloid dendritic cells reversibly impairs cytomegalovirus replication by inhibiting immediate early gene expression. J Virol (2015) 89(19):9886–95.10.1128/JVI.01459-15
    1. Paulus C, Krauss S, Nevels M. A human cytomegalovirus antagonist of type I IFN-dependent signal transducer and activator of transcription signaling. Proc Natl Acad Sci U S A (2006) 103(10):3840–5.10.1073/pnas.0600007103
    1. Phillips S, Mistry S, Riva A, Cooksley H, Hadzhiolova-Lebeau T, Plavova S, et al. Peg-interferon lambda treatment induces robust innate and adaptive immunity in chronic hepatitis B patients. Front Immunol (2017) 8:621.10.3389/fimmu.2017.00621
    1. Belloni L, Allweiss L, Guerrieri F, Pediconi N, Volz T, Pollicino T, et al. IFN-alpha inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome. J Clin Invest (2012) 122(2):529–37.10.1172/JCI58847
    1. Jiang J, Tang H. Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein. Protein Cell (2010) 1(12):1106–17.10.1007/s13238-010-0141-8
    1. Chen J, Wu M, Zhang X, Zhang W, Zhang Z, Chen L, et al. Hepatitis B virus polymerase impairs interferon-alpha-induced STA T activation through inhibition of importin-alpha5 and protein kinase C-delta. Hepatology (2013) 57(2):470–82.10.1002/hep.26064
    1. Griffiths SJ, Koegl M, Boutell C, Zenner HL, Crump CM, Pica F, et al. A systematic analysis of host factors reveals a Med23-interferon-lambda regulatory axis against herpes simplex virus type 1 replication. PLoS Pathog (2013) 9(8):e1003514.10.1371/journal.ppat.1003514
    1. Zhou L, Li JL, Zhou Y, Liu JB, Zhuang K, Gao JF, et al. Induction of interferon-lambda contributes to TLR3 and RIG-I activation-mediated inhibition of herpes simplex virus type 2 replication in human cervical epithelial cells. Mol Hum Reprod (2015) 21(12):917–29.10.1093/molehr/gav058
    1. Pica F, Volpi A, Gaziano R, Garaci E. Interferon-lambda in immunocompetent individuals with a history of recurrent herpes labialis. Antivir Ther (2010) 15(5):737–43.10.3851/IMP1610
    1. Wilcox DR, Folmsbee SS, Muller WJ, Longnecker R. The type I interferon response determines differences in choroid plexus susceptibility between newborns and adults in herpes simplex virus encephalitis. MBio (2016) 7(2):e00437–16.10.1128/mBio.00437-16
    1. McFarland AP, Horner SM, Jarret A, Joslyn RC, Bindewald E, Shapiro BA, et al. The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs. Nat Immunol (2014) 15(1):72–9.10.1038/ni.2758
    1. Jarret A, McFarland AP, Horner SM, Kell A, Schwerk J, Hong M, et al. Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling. Nat Med (2016) 22(12):1475–81.10.1038/nm.4211
    1. Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, Dickensheets H, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet (2013) 45(2):164–71.10.1038/ng.2521
    1. Hong M, Schwerk J, Lim C, Kell A, Jarret A, Pangallo J, et al. Interferon lambda 4 expression is suppressed by the host during viral infection. J Exp Med (2016) 213(12):2539–52.10.1084/jem.20160437
    1. Di Domizio J, Cao W. Fueling autoimmunity: type I interferon in autoimmune diseases. Expert Rev Clin Immunol (2013) 9(3):201–10.10.1586/eci.12.106
    1. Niewold TB. Type I interferon in human autoimmunity. Front Immunol (2014) 5:306.10.3389/fimmu.2014.00306
    1. Postal M, Sinicato NA, Pelicari KO, Marini R, Lavras Costallat LT, Appenzeller S. Clinical and serological manifestations associated with interferon-alpha levels in childhood-onset systemic lupus erythematosus. Clinics (Sao Paulo) (2012) 67(2):157–62.10.6061/clinics/2012(02)11
    1. Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon- alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol (2001) 159(1):237–43.10.1016/S0002-9440(10)61689-6
    1. Rowland SL, Riggs JM, Gilfillan S, Bugatti M, Vermi W, Kolbeck R, et al. Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model. J Exp Med (2014) 211(10):1977–91.10.1084/jem.20132620
    1. Sisirak V, Ganguly D, Lewis KL, Couillault C, Tanaka L, Bolland S, et al. Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. J Exp Med (2014) 211(10):1969–76.10.1084/jem.20132522
    1. Blazek K, Eames HL, Weiss M, Byrne AJ, Perocheau D, Pease JE, et al. IFN-lambda resolves inflammation via suppression of neutrophil infiltration and IL-1beta production. J Exp Med (2015) 212(6):845–53.10.1084/jem.20140995
    1. Broggi A, Tan Y, Granucci F, Zanoni I. IFN-lambda suppresses intestinal inflammation by non-translational regulation of neutrophil function. Nat Immunol (2017) 18:1084–93.10.1038/ni.3821
    1. Dantas AT, Goncalves SM, Pereira MC, de Almeida AR, Marques CD, Rego MJ, et al. Interferons and systemic sclerosis: correlation between interferon gamma and interferon-lambda 1 (IL-29). Autoimmunity (2015) 48(7):429–33.10.3109/08916934.2015.1054028
    1. Yin Z, Dai J, Deng J, Sheikh F, Natalia M, Shih T, et al. Type III IFNs are produced by and stimulate human plasmacytoid dendritic cells. J Immunol (2012) 189(6):2735–45.10.4049/jimmunol.1102038
    1. Finotti G, Tamassia N, Calzetti F, Fattovich G, Cassatella MA. Endogenously produced TNF-alpha contributes to the expression of CXCL10/IP-10 in IFN-lambda3-activated plasmacytoid dendritic cells. J Leukoc Biol (2016) 99(1):107–19.10.1189/jlb.3VMA0415-144R
    1. Martinez J, Huang X, Yang Y. Direct action of type I IFN on NK cells is required for their activation in response to vaccinia viral infection in vivo. J Immunol (2008) 180(3):1592–7.10.4049/jimmunol.180.3.1592
    1. Paolini R, Bernardini G, Molfetta R, Santoni A. NK cells and interferons. Cytokine Growth Factor Rev (2015) 26(2):113–20.10.1016/j.cytogfr.2014.11.003
    1. Madera S, Rapp M, Firth MA, Beilke JN, Lanier LL, Sun JC. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. J Exp Med (2016) 213(2):225–33.10.1084/jem.20150712
    1. Kramer B, Eisenhardt M, Glassner A, Korner C, Sauerbruch T, Spengler U, et al. Do lambda-IFNs IL28A and IL28B act on human natural killer cells? Proc Natl Acad Sci U S A (2011) 108(34):E519–20.10.1073/pnas.1108850108
    1. Souza-Fonseca-Guimaraes F, Young A, Mittal D, Martinet L, Bruedigam C, Takeda K, et al. NK cells require IL-28R for optimal in vivo activity. Proc Natl Acad Sci U S A (2015) 112(18):E2376–84.10.1073/pnas.1424241112
    1. Vadiveloo PK, Vairo G, Hertzog P, Kola I, Hamilton JA. Role of type I interferons during macrophage activation by lipopolysaccharide. Cytokine (2000) 12(11):1639–46.10.1006/cyto.2000.0766
    1. Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol (2014) 5:614.10.3389/fimmu.2014.00614
    1. Xie C, Liu C, Wu B, Lin Y, Ma T, Xiong H, et al. Effects of IRF1 and IFN-beta interaction on the M1 polarization of macrophages and its antitumor function. Int J Mol Med (2016) 38(1):148–60.10.3892/ijmm.2016.2583
    1. Montoya M, Schiavoni G, Mattei F, Gresser I, Belardelli F, Borrow P, et al. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood (2002) 99(9):3263–71.10.1182/blood.V99.9.3263
    1. Chen K, Liu J, Cao X. Regulation of type I interferon signaling in immunity and inflammation: a comprehensive review. J Autoimmun (2017) 83:1–11.10.1016/j.jaut.2017.03.008
    1. Liu BS, Janssen HL, Boonstra A. IL-29 and IFNalpha differ in their ability to modulate IL-12 production by TLR-activated human macrophages and exhibit differential regulation of the IFNgamma receptor expression. Blood (2011) 117(8):2385–95.10.1182/blood-2010-07-298976
    1. Dickensheets H, Sheikh F, Park O, Gao B, Donnelly RP. Interferon-lambda (IFN-lambda) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes. J Leukoc Biol (2013) 93(3):377–85.10.1189/jlb.0812395
    1. de Groen RA, Boltjes A, Hou J, Liu BS, McPhee F, Friborg J, et al. IFN-lambda-mediated IL-12 production in macrophages induces IFN-gamma production in human NK cells. Eur J Immunol (2015) 45(1):250–9.10.1002/eji.201444903
    1. Mennechet FJ, Uze G. Interferon-lambda-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells. Blood (2006) 107(11):4417–23.10.1182/blood-2005-10-4129
    1. Swiecki M, Colonna M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol (2015) 15(8):471–85.10.1038/nri3865
    1. Finotti G, Tamassia N, Cassatella MA. Interferon-lambdas and plasmacytoid dendritic cells: a close relationship. Front Immunol (2017) 8:1015.10.3389/fimmu.2017.01015
    1. del Rio ML, Bernhardt G, Rodriguez-Barbosa JI, Forster R. Development and functional specialization of CD103+ dendritic cells. Immunol Rev (2010) 234(1):268–81.10.1111/j.0105-2896.2009.00874.x
    1. Ho AW, Prabhu N, Betts RJ, Ge MQ, Dai X, Hutchinson PE, et al. Lung CD103+ dendritic cells efficiently transport influenza virus to the lymph node and load viral antigen onto MHC class I for presentation to CD8 T cells. J Immunol (2011) 187(11):6011–21.10.4049/jimmunol.1100987
    1. Neyt K, Lambrecht BN. The role of lung dendritic cell subsets in immunity to respiratory viruses. Immunol Rev (2013) 255(1):57–67.10.1111/imr.12100
    1. Moltedo B, Li W, Yount JS, Moran TM. Unique type I interferon responses determine the functional fate of migratory lung dendritic cells during influenza virus infection. PLoS Pathog (2011) 7(11):e1002345.10.1371/journal.ppat.1002345
    1. Heng TS, Painter MW, Immunological Genome Project Consortium . The Immunological Genome Project: networks of gene expression in immune cells. Nat Immunol (2008) 9(10):1091–4.10.1038/ni1008-1091
    1. Kasimir S, Brom J, Konig W. Effect of interferon-alpha on neutrophil functions. Immunology (1991) 74(2):271–8.
    1. Camp JV, Jonsson CB. A role for neutrophils in viral respiratory disease. Front Immunol (2017) 8:550.10.3389/fimmu.2017.00550
    1. Hemann EA, Schwerk J, Savan R. IFN-lambda ‘guts’ neutrophil-mediated inflammation. Nat Immunol (2017) 18(10):1061–2.10.1038/ni.3834
    1. de Groen RA, Groothuismink ZM, Liu BS, Boonstra A. IFN-lambda is able to augment TLR-mediated activation and subsequent function of primary human B cells. J Leukoc Biol (2015) 98(4):623–30.10.1189/jlb.3A0215-041RR
    1. Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, et al. IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques. Mol Ther (2010) 18(9):1714–23.10.1038/mt.2010.118
    1. Crouse J, Kalinke U, Oxenius A. Regulation of antiviral T cell responses by type I interferons. Nat Rev Immunol (2015) 15(4):231–42.10.1038/nri3806

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