NK cells participate in innate immune responses by secreting gamma interferon (IFN-γ) and by destroying virus-infected cells. Here the interaction between influenza A or Sendai virus-infected macrophages and NK cells has been studied. A rapid, cell–cell contact-dependent production of IFN-γ from NK cells cultured with virus-infected macrophages was observed. Expression of the MHC class I-related chain B (MICB) gene, a ligand for NK cell-activating receptor NKG2D, was upregulated in virus-infected macrophages suggesting a role for MICB in the activation of the IFN-γ gene in NK cells. IL12Rβ2, IL18R and T-bet mRNA synthesis was enhanced in NK cells cultured with virus-infected macrophages. Upregulation of these genes was dependent on macrophage-derived IFN-α. In contrast to IL12Rβ2, expression of WSX-1/TCCR, a receptor for IL27, was reduced in NK cells in response to virus-induced IFN-α. In conclusion, these results show that virus-infected macrophages activate NK cells via cytokines and direct cellular interactions and further emphasize the role of IFN-α in the activation of innate immunity.
AfkarianM.,
SedyJ. R.,
YangJ.,
JacobsonN. G.,
CerebN.,
YangS. Y.,
MurphyT. L.,
MurphyK. M.2002; T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3:549–557
BauerS.,
GrohV.,
WuJ.,
SteinleA.,
PhillipsJ. H.,
LanierL. L.,
SpiesT.1999; Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729[CrossRef]
BironC. A.1998; Role of early cytokines, including alpha and beta interferons (IFN- α / β ), in innate and adaptive immune responses to viral infections. Semin Immunol 10:383–390[CrossRef]
BironC. A.,
ByronK. S.,
SullivanJ. L.1989; Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320:1731–1735[CrossRef]
BironC. A.,
NguyenK. B.,
PienG. C.,
CousensL. P.,
Salazar-MatherT. P.1999; Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220[CrossRef]
ChenQ.,
GhilardiN.,
WangH.,
BakerT.,
XieM. H.,
GurneyA.,
GrewalI. S.,
de SauvageF. J.2000; Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407:916–920[CrossRef]
CuaD. J.,
SherlockJ.,
ChenY.13 other authors2003; Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748[CrossRef]
FerlazzoG.,
TsangM. L.,
MorettaL.,
MelioliG.,
SteinmanR. M.,
MunzC.2002; Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 195:343–351[CrossRef]
Garcia-SastreA.,
EgorovA.,
MatassovD.,
BrandtS.,
LevyD. E.,
DurbinJ. E.,
PaleseP.,
MusterT.1998; Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252:324–330[CrossRef]
GongJ. H.,
MakiG.,
KlingemannH. G.1994; Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia 8:652–658
HunterC. A.,
TimansJ.,
PisacaneP.7 other authors1997; Comparison of the effects of interleukin-1 α , interleukin-1 β and interferon- γ -inducing factor on the production of interferon- γ by natural killer. Eur J Immunol 27:2787–2792[CrossRef]
JinushiM.,
TakeharaT.,
KantoT.7 other authors2003; Critical role of MHC class I-related chain A and B expression on IFN- α -stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection. J Immunol 170:1249–1256[CrossRef]
LighvaniA. A.,
FruchtD. M.,
JankovicD.8 other authors2001; T-bet is rapidly induced by interferon- γ in lymphoid and myeloid cells. Proc Natl Acad Sci U S A 98:15137–15142[CrossRef]
MandelboimO.,
LiebermanN.,
LevM.7 other authors2001; Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature 409:1055–1060[CrossRef]
MatikainenS.,
PaananenA.,
MiettinenM.,
KurimotoM.,
TimonenT.,
JulkunenI.,
SarenevaT.2001; IFN- α and IL-18 synergistically enhance IFN- γ production in human NK cells: differential regulation of Stat4 activation and IFN- γ gene expression by IFN- α and IL-12. Eur J Immunol 31:2236–2245[CrossRef]
MicallefM. J.,
OhtsukiT.,
KohnoK.9 other authors1996; Interferon- γ -inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon- γ production. Eur J Immunol 26:1647–1651[CrossRef]
NguyenK. B.,
Salazar-MatherT. P.,
DalodM. Y.,
Van DeusenJ. B.,
WeiX. Q.,
LiewF. Y.,
CaligiuriM. A.,
DurbinJ. E.,
BironC. A.2002; Coordinated and distinct roles for IFN- αβ , IL-12 and IL-15 regulation of NK cell responses to viral infection. J Immunol 169:4279–4287[CrossRef]
OppmannB.,
LesleyR.,
BlomB.22 other authors2000; Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725[CrossRef]
OrangeJ. S.,
BironC. A.1996; An absolute and restricted requirement for IL-12 in natural killer cell IFN- γ production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections. J Immunol 156:1138–1142
ParhamC.,
ChiricaM.,
TimansJ.19 other authors2002; A receptor for the heterodimeric cytokine IL-23 is composed of IL-12R β 1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168:5699–5708[CrossRef]
PflanzS.,
TimansJ. C.,
CheungJ.18 other authors2002; IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity 16:779–790[CrossRef]
PirhonenJ.,
SarenevaT.,
KurimotoM.,
JulkunenI.,
MatikainenS.1999; Virus infection activates IL-1 β and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol 162:7322–7329
PirhonenJ.,
SarenevaT.,
JulkunenI.,
MatikainenS.2001; Virus infection induces proteolytic processing of IL-18 in human macrophages via caspase-1 and caspase-3 activation. Eur J Immunol 31:726–733[CrossRef]
PirhonenJ.,
MatikainenS.,
JulkunenI.2002; Regulation of virus-induced IL-12 and IL-23 expression in human macrophages. J Immunol 169:5673–5678[CrossRef]
RoggeL.,
Barberis-MainoL.,
BiffiM.,
PassiniN.,
PreskyD. H.,
GublerU.,
SinigagliaF.1997; Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 185:825–831[CrossRef]
SarenevaT.,
PirhonenJ.,
CantellK.,
KalkkinenN.,
JulkunenI.1994; Role of N -glycosylation in the synthesis, dimerization and secretion of human interferon- γ
. Biochem J 303:831–840
SarenevaT.,
JulkunenI.,
MatikainenS.2000; IFN- α and IL-12 induce IL-18 receptor gene expression in human NK and T cells. J Immunol 165:1933–1938[CrossRef]
SpaggiariG. M.,
CarosioR.,
PendeD.,
MarcenaroS.,
RiveraP.,
ZocchiM. R.,
MorettaL.,
PoggiA.2001; NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46. Eur J Immunol 31:1656–1665[CrossRef]
SzaboS. J.,
SullivanB. M.,
StemmannC.,
SatoskarA. R.,
SleckmanB. P.,
GlimcherL. H.2002; Distinct effects of T-bet in TH1 lineage commitment and IFN- γ production in CD4 and CD8 T cells. Science 295:338–342[CrossRef]
TrinchieriG.1997; Cytokines acting on or secreted by macrophages during intracellular infection (IL-10, IL-12, IFN- γ ). Curr Opin Immunol 9:17–23[CrossRef]
WangX.,
LiM.,
ZhengH.,
MusterT.,
PaleseP.,
BegA. A.,
Garcia-SastreA.2000; Influenza A virus NS1 protein prevents activation of NF- κ B and induction of α / β interferon. J Virol 74:11566–11573[CrossRef]