Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

PLoS Pathogens

Volumn 9, Issue 7, 2013, Pages

  Kader, Muhamuda ^a   Smith, Amanda P ^a   Guiducci, Cristiana ^b   Wonderlich, Elizabeth R ^a   Normolle, Daniel ^c   Watkins, Simon C ^d   Barrat, Franck J ^b,e   Barratt Boyes, Simon M ^a,d  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b Dynavax Technologies Corporation   (United States)

^c UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^d UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^e HOSPITAL FOR SPECIAL SURGERY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; ALPHA INTERFERON; CHEMOKINE RECEPTOR CCR7; DV056; INTERFERON REGULATORY FACTOR 7; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL MODEL; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; CELL STIMULATION; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; IMMUNOFLUORESCENCE TEST; INNATE IMMUNITY; LYMPH NODE CELL; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PLASMACYTOID DENDRITIC CELL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RHESUS MONKEY; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; VIRUS LOAD;

EID: 84883821864     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003530     Document Type: Article

References (71)

1. Sodora DL, Silvestri G, (2008) Immune activation and AIDS pathogenesis. Aids 22: 439-446.
2. Chahroudi A, Bosinger SE, Vanderford TH, Paiardini M, Silvestri G, (2012) Natural SIV hosts: showing AIDS the door. Science 335: 1188-1193.
3. Letvin NL, Daniel MD, Sehgal PK, Desrosiers RC, Hunt RD, et al. (1985) Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science 230: 71-73.
4. Murphey-Corb M, Martin LN, Rangan SR, Baskin GB, Gormus BJ, et al. (1986) Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature 321: 435-437.
5. Estaquier J, Idziorek T, de Bels F, Barre-Sinoussi F, Hurtrel B, et al. (1994) Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. Proc Natl Acad Sci U S A 91: 9431-9435.
6. Kornfeld C, Ploquin MJ, Pandrea I, Faye A, Onanga R, et al. (2005) Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 115: 1082-1091.
7. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 1365-1371.
8. Silvestri G, Sodora DL, Koup RA, Paiardini M, O'Neil SP, et al. (2003) Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18: 441-452.
9. Pandrea I, Apetrei C, Dufour J, Dillon N, Barbercheck J, et al. (2006) Simian immunodeficiency virus SIVagm.sab infection of Caribbean African green monkeys: a new model for the study of SIV pathogenesis in natural hosts. J Virol 80: 4858-4867.
10. Pandrea IV, Gautam R, Ribeiro RM, Brenchley JM, Butler IF, et al. (2007) Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol 179: 3035-3046.
11. Favre D, Lederer S, Kanwar B, Ma ZM, Proll S, et al. (2009) Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog 5: e1000295.
12. Estes JD, Gordon SN, Zeng M, Chahroudi AM, Dunham RM, et al. (2008) Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques. J Immunol 180: 6798-6807.
13. Bosinger SE, Li Q, Gordon SN, Klatt NR, Duan L, et al. (2009) Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 119: 3556-3572.
14. Jacquelin B, Mayau V, Targat B, Liovat AS, Kunkel D, et al. (2009) Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J Clin Invest 119: 3544-3555.
15. Lederer S, Favre D, Walters KA, Proll S, Kanwar B, et al. (2009) Transcriptional profiling in pathogenic and non-pathogenic SIV infections reveals significant distinctions in kinetics and tissue compartmentalization. PLoS Pathog 5: e1000296.
16. Campillo-Gimenez L, Laforge M, Fay M, Brussel A, Cumont MC, et al. (2010) Non pathogenesis of SIV infection is associated with reduced inflammation and recruitment of plasmacytoid dendritic cells to lymph nodes, not to lack of an interferon type I response, during the acute phase. J Virol 84: 1838-1846.
17. Harris LD, Tabb B, Sodora DL, Paiardini M, Klatt NR, et al. (2010) 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 84: 7886-7891.
18. Bosinger SE, Sodora DL, Silvestri G, (2011) Generalized immune activation and innate immune responses in simian immunodeficiency virus infection. Curr Opin HIV AIDS 6: 411-418.
19. Mir KD, Gasper MA, Sundaravaradan V, Sodora DL, (2011) SIV infection in natural hosts: resolution of immune activation during the acute-to-chronic transition phase. Microbes Infect 13: 14-24.
20. Fitzgerald-Bocarsly P, Jacobs ES, (2010) Plasmacytoid dendritic cells in HIV infection: striking a delicate balance. J Leukoc Biol 87: 609-620.
21. Feldman S, Stein D, Amrute S, Denny T, Garcia Z, et al. (2001) Decreased interferon-alpha production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors. Clin Immunol 101: 201-210.
22. Soumelis V, Scott I, Gheyas F, Bouhour D, Cozon G, et al. (2001) Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 98: 906-912.
23. Brown KN, Trichel A, Barratt-Boyes SM, (2007) Parallel loss of myeloid and plasmacytoid dendritic cells from blood and lymphoid tissue in simian AIDS. J Immunol 178: 6958-6967.
24. Malleret B, Maneglier B, Karlsson I, Lebon P, Nascimbeni M, et al. (2008) Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood 112: 4598-4608.
25. Brown KN, Wijewardana V, Liu X, Barratt-Boyes SM, (2009) Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection. PLoS Pathog 5: e1000413.
26. Kwa S, Kannanganat S, Nigam P, Siddiqui M, Shetty RD, et al. (2011) Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques. Blood 118: 2763-2773.
27. Reeves RK, Evans TI, Gillis J, Wong FE, Kang G, et al. (2012) SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa. J Infect Dis 206: 1462-1468.
28. Herbeuval JP, Hardy AW, Boasso A, Anderson SA, Dolan MJ, et al. (2005) Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells. Proc Natl Acad Sci U S A 102: 13974-13979.
29. Herbeuval JP, Nilsson J, Boasso A, Hardy AW, Kruhlak MJ, et al. (2006) Differential expression of IFN-alpha and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients. Proc Natl Acad Sci U S A 103: 7000-7005.
30. Sedaghat AR, German J, Teslovich TM, Cofrancesco J Jr, Jie CC, et al. (2008) Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics. J Virol 82: 1870-1883.
31. Boasso A, Royle CM, Doumazos S, Aquino VN, Biasin M, et al. (2011) Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood 118: 5152-5162.
32. O'Brien M, Manches O, Sabado RL, Jimenez Baranda S, Wang Y, et al. (2011) Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-alpha-producing and partially matured phenotype. J Clin Invest 121: 1088-1101.
33. Boasso A, Shearer GM, (2008) Chronic innate immune activation as a cause of HIV-1 immunopathogenesis. Clin Immunol 126: 235-242.
34. Ellegard R, Shankar EM, Larsson M, (2011) Targeting HIV-1 innate immune responses therapeutically. Curr Opin HIV AIDS 6: 435-443.
35. Ries M, Pritschet K, Schmidt B, (2012) Blocking type I interferon production: a new therapeutic option to reduce the HIV-1-induced immune activation. Clin Dev Immunol 2012: 534929.
36. Beignon AS, McKenna K, Skoberne M, Manches O, DaSilva I, et al. (2005) Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 115: 3265-3275.
37. Mandl JN, Barry AP, Vanderford TH, Kozyr N, Chavan R, et al. (2008) Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med 14: 1077-1087.
38. Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, et al. (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202: 1131-1139.
39. Barrat FJ, Meeker T, Chan JH, Guiducci C, Coffman RL, (2007) Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur J Immunol 37: 3582-3586.
40. Guiducci C, Tripodo C, Gong M, Sangaletti S, Colombo MP, et al. (2010) Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9. J Exp Med 207: 2931-2942.
41. Brown KN, Barratt-Boyes SM, (2009) Surface phenotype and rapid quantification of blood dendritic cell subsets in the rhesus macaque. J Med Primatol 38: 272-278.
42. Pichlmair A, Reis e Sousa C, (2007) Innate recognition of viruses. Immunity 27: 370-383.
43. Wonderlich ER, Wijewardana V, Liu X, Barratt-Boyes SM, (2013) Virus-encoded TLR ligands reveal divergent functional responses of mononuclear phagocytes in pathogenic simian immunodeficiency virus infection. J Immunol 190: 2188-2198.
44. Honda K, et al. (2005) IRF-7 is the master regulator of type-1 interferon-dependent immune responses. Nature 434: 772-777.
45. Picker LJ, Hagen SI, Lum R, Reed-Inderbitzin EF, Daly LM, et al. (2004) Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med 200: 1299-1314.
46. Monceaux V, Viollet L, Petit F, Ho Tsong Fang R, Cumont MC, et al. (2005) CD8+ T cell dynamics during primary simian immunodeficiency virus infection in macaques: relationship of effector cell differentiation with the extent of viral replication. J Immunol 174: 6898-6908.
47. Shedlock DJ, Silvestri G, Weiner DB, (2009) Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials. Nat Rev Immunol 9: 717-728.
48. Nascimbeni M, Perie L, Chorro L, Diocou S, Kreitmann L, et al. (2009) Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-alpha expression. Blood 113: 6112-6119.
49. Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, et al. (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206: 1589-1602.
50. Swiecki M, Gilfillan S, Vermi W, Wang Y, Colonna M, (2010) Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity 33: 955-966.
51. Levy DE, Marie IJ, Durbin JE, (2011) Induction and function of type I and III interferon in response to viral infection. Curr Opin Virol 1: 476-486.
52. Vanderford TH, Slichter C, Rogers KA, Lawson BO, Obaede R, et al. (2012) Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation. Blood 119: 5750-5757.
53. Tavel JA, Huang CY, Shen J, Metcalf JA, Dewar R, et al. (2010) Interferon-alpha produces significant decreases in HIV load. J Interferon Cytokine Res 30: 461-464.
54. Manion M, Rodriguez B, Medvik K, Hardy G, Harding CV, et al. (2012) Interferon-alpha administration enhances CD8+ T cell activation in HIV infection. PLoS One 7: e30306.
55. Estes JD, Harris LD, Klatt NR, Tabb B, Pittaluga S, et al. (2010) Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog 6: e1001052.
56. Dutertre CA, Amraoui S, Derosa A, Jourdain JP, Vimeux L, et al. (2012) Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFalpha overproduction in response to microbial products. Blood 120: 2259-2268.
57. Biancotto A, Grivel JC, Iglehart SJ, Vanpouille C, Lisco A, et al. (2007) Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood 109: 4272-4279.
58. Estes JD, Li Q, Reynolds MR, Wietgrefe S, Duan L, et al. (2006) Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J Infect Dis 193: 703-712.
59. Katsikis PD, Mueller YM, Villinger F, (2011) The cytokine network of acute HIV infection: a promising target for vaccines and therapy to reduce viral set-point? PLoS Pathog 7: e1002055.
60. Geary RS, Leeds JM, Henry SP, Monteith DK, Levin AA, (1997) Antisense oligonucleotide inhibitors for the treatment of cancer: 1. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides. Anticancer Drug Des 12: 383-393.
61. Geary RS, Yu RZ, Watanabe T, Henry SP, Hardee GE, et al. (2003) Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2′-O-(2-methoxyethyl) modified antisense oligonucleotide: comparison across species. Drug Metab Dispos 31: 1419-1428.
62. Monteith DK, Horner MJ, Gillett NA, Butler M, Geary R, et al. (1999) Evaluation of the renal effects of an antisense phosphorothioate oligodeoxynucleotide in monkeys. Toxicol Pathol 27: 307-317.
63. Monteith DK, Levin AA, (1999) Synthetic oligonucleotides: the development of antisense therapeutics. Toxicol Pathol 27: 8-13.
64. Phillips JA, Craig SJ, Bayley D, Christian RA, Geary R, et al. (1997) Pharmacokinetics, metabolism, and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration. Biochem Pharmacol 54: 657-668.
65. Hardy AW, Graham DR, Shearer GM, Herbeuval JP, (2007) HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-alpha. Proc Natl Acad Sci U S A 104: 17453-17458.
66. Fiorentini S, Riboldi E, Facchetti F, Avolio M, Fabbri M, et al. (2008) HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype. Proc Natl Acad Sci U S A 105: 3867-3872.
67. Orendi JM, Bloem AC, Borleffs JC, Wijnholds FJ, de Vos NM, et al. (1998) Activation and cell cycle antigens in CD4+ and CD8+ T cells correlate with plasma human immunodeficiency virus (HIV-1) RNA level in HIV-1 infection. J Infect Dis 178: 1279-1287.
68. Sachsenberg N, Perelson AS, Yerly S, Schockmel GA, Leduc D, et al. (1998) Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med 187: 1295-1303.
69. Hackl D, Loschko J, Sparwasser T, Reindl W, Krug AB, (2011) Activation of dendritic cells via TLR7 reduces Foxp3 expression and suppressive function in induced Tregs. Eur J Immunol 41: 1334-1343.
70. Pasare C, Medzhitov R, (2004) Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21: 733-741.
71. Hirotsu C, Srivastava M, (2000) Simultaneous confidence intervals based on one-sided max t test. Stat Prob Letters 49: 25-37.