HSV-1-induced chemokine expression via IFI16-dependent and IFI16-independent pathways in human monocyte-derived macrophages

Herpesviridae

Jesper Melchjorsen¹  Lars Østergaard¹  Rune R Laursen¹  Stine Søby¹ 

[1] Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, Aarhus N, DK-8200, Denmark

关键词: Human;    Macrophages;    DNA;    PRR;    Chemokine;    IFI16;    Innate;    Herpes simplex virus;   

Others  :  801032
DOI  :  10.1186/2042-4280-3-6

 received in 2012-05-16, accepted in 2012-10-04,  发布年份 2012

【 摘 要 】

Background

Innate recognition is essential in the antiviral response against infection by herpes simplex virus (HSV). Chemokines are important for control of HSV via recruitment of natural killer cells, T lymphocytes, and antigen-presenting cells. We previously found that early HSV-1-mediated chemokine responses are not dependent on TLR2 and TLR9 in human macrophages. Here, we investigated the role of the recently identified innate IFN-inducible DNA receptor IFI16 during HSV-1 infection in human macrophages.

Methods

Peripheral blood mononuclear cells were purified from buffy coats and monocytes were differentiated to macrophages. Macrophages infected with HSV-1 were analyzed using siRNA-mediated knock-down of IFI16 by real-time PCR, ELISA, and Western blotting.

Results

We determined that both CXCL10 and CCL3 are induced independent of HSV-1 replication. IFI16 mediates CCL3 mRNA accumulation during early HSV-1 infection. In contrast, CXCL10 was induced independently of IFI16.

Conclusions

Our data provide the first evidence of HSV-1-induced innate immune responses via IFI16 in human primary macrophages. In addition, the data suggest that at least one additional unidentified receptor or innate sensing mechanism is involved in recognizing HSV-1 prior to viral replication.

【 授权许可】

   
2012 Søby et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Rozenberg F, Deback C, Agut H: Herpes simplex encephalitis: from virus to therapy. Infect Disord Drug Targets 2011, 11:235-250.
• [2]Whitley RJ: Herpes simplex encephalitis: adolescents and adults. Antiviral Res 2006, 71:141-148.
• [3]Carr DJ, Harle P, Gebhardt BM: The immune response to ocular herpes simplex virus type 1 infection. Exp Biol Med (Maywood) 2001, 226:353-366.
• [4]Melchjorsen J, Paludan SR: Induction of RANTES/CCL5 by herpes simplex virus is regulated by nuclear factor kappa B and interferon regulatory factor 3. J Gen Virol 2003, 84:2491-2495.
• [5]Melchjorsen J, Siren J, Julkunen I, Paludan SR, Matikainen S: Induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by ICP27 targeting NF-kappaB and IRF-3. J Gen Virol 2006, 87:1099-1108.
• [6]Thapa M, Welner RS, Pelayo R, Carr DJ: CXCL9 and CXCL10 expression are critical for control of genital herpes simplex virus type 2 infection through mobilization of HSV-specific CTL and NK cells to the nervous system. J Immunol 2008, 180:1098-1106.
• [7]Liu T, Khanna KM, Chen X, Fink DJ, Hendricks RL: CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons. J Exp Med 2000, 191:1459-1466.
• [8]Rager-Zisman B, Quan PC, Rosner M, Moller JR, Bloom BR: Role of NK cells in protection of mice against herpes simplex virus-1 infection. J Immunol 1987, 138:884-888.
• [9]Thapa M, Kuziel WA, Carr DJ: Susceptibility of CCR5-deficient mice to genital herpes simplex virus type 2 is linked to NK cell mobilization. J Virol 2007, 81:3704-3713.
• [10]Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S: Macrophage receptors and immune recognition. Annu Rev Immunol 2005, 23:901-944.
• [11]Matikainen S, Pirhonen J, Miettinen M, Lehtonen A, Govenius-Vintola C, Sareneva T, et al.: Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. Virology 2000, 276:138-147.
• [12]Ellermann-Eriksen S: Macrophages and cytokines in the early defence against herpes simplex virus. Virol J 2005, 2:59. BioMed Central Full Text
• [13]Mosser DM, Edwards JP: Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008, 8:958-969.
• [14]Melchjorsen J: Sensing herpes: more than toll. Rev Med Virol 2012, 22:106-121.
• [15]Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, et al.: Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A 2004, 101:1315-1320.
• [16]Aravalli RN, Hu S, Rowen TN, Palmquist JM, Lokensgard JR: Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus. J Immunol 2005, 175:4189-4193.
• [17]Leoni V, Gianni T, Salvioli S, Campadelli-Fiume G: Herpes Simplex Virus Glycoproteins gH/gL and gB Bind Toll-Like Receptor 2, and Soluble gH/gL Is Sufficient To Activate NF-kappaB. J Virol 2012, 86:6555-6562.
• [18]Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, et al.: TLR3 deficiency in patients with herpes simplex encephalitis. Science 2007, 317:1522-1527.
• [19]Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A: Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 2003, 198:513-520.
• [20]Malmgaard L, Melchjorsen J, Bowie AG, Mogensen SC, Paludan SR: Viral activation of macrophages through TLR-dependent and -independent pathways. J Immunol 2004, 173:6890-6898.
• [21]Hochrein H, Schlatter B, O'Keeffe M, Wagner C, Schmitz F, Schiemann M, et al.: Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and -independent pathways. Proc Natl Acad Sci U S A 2004, 101:11416-11421.
• [22]Melchjorsen J, Rintahaka J, Soby S, Horan KA, Poltajainen A, Ostergaard L, et al.: Early innate recognition of herpes simplex virus in human primary macrophages is mediated via the MDA5/MAVS-dependent and MDA5/MAVS/RNA polymerase III-independent pathways. J Virol 2010, 84:11350-11358.
• [23]Holm CK, Jensen SB, Jakobsen MR, Cheshenko N, Horan KA, Moeller HB, et al.: Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat Immunol 2012, 13:737-743.
• [24]Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, et al.: IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 2010, 11:997-1004.
• [25]Rasmussen SB, Sorensen LN, Malmgaard L, Ank N, Baines JD, Chen ZJ, et al.: Type I IFN production during herpes simplex virus infection is controlled by cell-type specific viral recognition through TLR9, the MAVS pathway, and novel recognition systems. J Virol 2007, 81:13315-13324.
• [26]Melchjorsen J, Kristiansen H, Christiansen R, Rintahaka J, Matikainen S, Paludan SR, et al.: Differential Regulation of the OASL and OAS1 Genes in Response to Viral Infections. J Interferon Cytokine Res 2009, 29:199-207.
• [27]Melchjorsen J, Matikainen S: Paludan SR:Activation and Evasion of Innate Antiviral Immunity by Herpes Simplex Virus. Viruses 2009, 1:737-759.
• [28]Paladino P, Mossman KL: Mechanisms Employed by HSV-1 to Inhibit the Interferon Response. J Interferon Cytokine Res 2009, 29:599-607.
• [29]Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, et al.: DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007, 448:501-505.
• [30]Ciesielski CJ, Andreakos E, Foxwell BM, Feldmann M: TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion. Eur J Immunol 2002, 32:2037-2045.
• [31]Gariano GR, Dell'Oste V, Bronzini M, Gatti D, Luganini A, Andrea MD, et al.: The intracellular DNA sensor IFI16 gene acts as restriction factor for human cytomegalovirus replication. PLoS Pathog 2012, 8:e1002498.
• [32]Collins SE, Noyce RS, Mossman KL: Innate cellular response to virus particle entry requires IRF3 but not virus replication. J Virol 2004, 78:1706-1717.
• [33]Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu YJ: The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol 2011, 12:959-965.
• [34]Miyashita M, Oshiumi H, Matsumoto M, Seya T: DDX60, a DExD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling. Mol Cell Biol 2011, 31:3802-3819.
• [35]Kim T, Pazhoor S, Bao M, Zhang Z, Hanabuchi S, Facchinetti V, et al.: Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc Natl Acad Sci U S A 2010, 107:15181-15186.
• [36]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, 186:4541-4545.
• [37]Iwasaki A: Antiviral immune responses in the genital tract: clues for vaccines. Nat Rev Immunol 2010, 10:699-711.
• [38]Bernstein DI, Earwood JD, Bravo FJ, Cohen GH, Eisenberg RJ, Clark JR, et al.: Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig. Vaccine 2011, 29:2071-2078.
• [39]Bernstein DI, Farley N, Bravo FJ, Earwood J, McNeal M, Fairman J, et al.: The adjuvant CLDC increases protection of a herpes simplex type 2 glycoprotein D vaccine in guinea pigs. Vaccine 2010, 28:3748-3753.
• [40]Bernstein DI, Cardin RD, Bravo FJ, Strasser JE, Farley N, Chalk C, et al.: Potent adjuvant activity of cationic liposome-DNA complexes for genital herpes vaccines. Clin Vaccine Immunol 2009, 16:699-705.