The Journal of Allergy and Clinical Immunology
Volume 116, Issue 6 , Pages 1334-1342 , December 2005

Innate immunity for biodefense: A strategy whose time has come

  • Catherine Amlie-Lefond, MD

      Affiliations

    • From the Department of Neurology, Medial College of Wisconsin
    • ,
  • David A. Paz, BS

      Affiliations

    • From the Department of Neurology, Medial College of Wisconsin
    • ,
  • Mary P. Connelly, BS

      Affiliations

    • From the Department of Neurology, Medial College of Wisconsin
    • ,
  • Gary B. Huffnagle, PhD

      Affiliations

    • Department of Internal Medicine and Microbiology and Immunology, University of Michigan
    • ,
  • Kyle S. Dunn, BS

      Affiliations

    • Center for Technology and National Security Policy, National Defense University, Washington, DC
    • ,
  • Noel T. Whelan, MS

      Affiliations

    • From the Department of Neurology, Medial College of Wisconsin
    • ,
  • Harry T. Whelan, MD

      Affiliations

    • From the Department of Neurology, Medial College of Wisconsin
    • Corresponding Author InformationReprint requests: Harry T. Whelan, MD, Bleser Professor of Neurology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.

Received 20 June 2005 ,Revised 10 August 2005 ,Accepted 11 August 2005.

References 

  1. Hackett CJ. Innate immune activation as a broad spectrum biodefense strategy: prospects and research challenges. J Allergy Clin Immunol. 2003;112:686–694
  2. Cox JT, Petry KU, Rylander E, Roy M. Using imiquimod for genital warts in female patients. J Womens Health (Larchmt). 2004;133:265–271
  3. Theos AU, Cummins R, Silverberg NB, Paller AS. Effectiveness of imiquimod cream 5% for treating childhood molluscum contagiosum in a double-blind, randomized pilot trial. Cutis. 2004;74:134–138141-2
  4. Arevalo I, Ward B, Miller R, Meng TC, Nagar E, Alvarez E, et al. Successful treatment of drug-resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis. 2001;33:1847–1851
  5. Krug A, Rothenfusser S, Hornung V, Jahrsdorfer B, Blackwell S, Ballas ZK, et al. Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur J Immunol. 2001;31:2154–2163
  6. Gursel M, Verthelyi D, Klinman DM. CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells. Eur J Immunol. 2002;32:2617–2622
  7. Vollmer J, Weeratna R, Payette P, Jurk M, Schetter C, Laucht M, et al. Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol. 2004;34:251–262
  8. Obermeier F, Dunger N, Deml L, Herfarth H, Scholmerich J, Falk W. CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice. Eur J Immunol. 2002;32:2084–2092
  9. Grajkowski A, Pedras-Vasconcelos J, Wang V, Ausin C, Hess S, Verthelyi D, et al. Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs. Nucleic Acids Res. 2005;33:3550–3560
  10. Klinman DM. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol. 2004;4:249–259
  11. Verthelyi D, Gursel M, Kenney RT, Lifson JD, Liu S, Mican J, et al. CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. J Immunol. 2003;170:4717–4723
  12. Leifer CA, Verthelyi D, Klinman DM. Heterogeneity in the human response to immunostimulatory CpG oligodeoxynucleotides. J Immunother. 2003;26:313–319
  13. Wang D, Kandimalla ER, Yu D, Tang JX, Agrawal S. Oral administration of second generation immunomodulatory oligonucleotides induces mucosal Th1 immune responses and adjuvant activity. Vaccine. 2005;23:2614–2622
  14. Kandimalla ER, Bhagat B, Li Y, Yu D, Wang D, Cong YP, et al. Immunomodulatory oligonucleotides containing a cytosine-phosphate-2′-deoxy-7-deazaguanosine motif as potent Toll-like receptor 9 agonists. Proc Natl Acad Sci U S A. 2005;102:6925–6930
  15. Billich A. Thymosin alpha1. SciClone Pharmaceuticals. Curr Opin Investig Drugs. 2002;3:698–707
  16. Romani L, Bistoni F, Gaziano R, Bozza S, Montagnoli C, Perruccio K, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103:4232–4239
  17. Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol. 2004;31:358–364
  18. Padalko E, Nuyens D, De Palma A, Verbeken E, Aerts JL, De Clercq E, et al. The interferon inducer ampligen [Poly(I)-Poly (C12U)] markedly protects mice against coxsackie B3 virus-induced myocarditis. Antimicrob Agents Chemother. 2004;48:267–274
  19. Cluff CW, Baldridge JR, Stöver AG, Evans JT, Johnson DA, Lacy MJ, et al. Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious challenge. Infect Immun. 2005;73:3044–3052
  20. Stöver AG, Da Silva Correia J, Evans JT, Cluff CW, Elliott MW, Jeffery EW, et al. Structure-activity relationship of synthetic toll-like receptor 4 agonists. J Biol Chem. 2004;279:4440–4449
  21. Hahm B, Trifilo MJ, Zuniga EI, Oldstone MB. Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling. Immunity. 2005;22:247–257
  22. Nishiwaki T, Yoneyama H, Eishi Y, Matsuo N, Tatsumi K, Kimura H, et al. Indigenous pulmonary propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice. Am J Pathol. 2004;165:631–639
  23. Matthews SJ, McCoy C. Peginterferon alfa-2a: a review of approved and investigational uses. Clin Ther. 2004;26:991–1025
  24. Liu G, Zhai Q, Schaffner DJ, Wu A, Yohannes A, Robinson TM, et al. Prevention of lethal respiratory vaccinia infections in mice with interferon-alpha and interferon-gamma. FEMS Immunol Med Microbiol. 2004;40:201–206
  25. Sperber SJ, Hayden FG. Antiviral chemotherapy and prophylaxis of viral respiratory disease. Clin Lab Med. 1987;7:869–896
  26. Hayden FG. Clinical applications of antiviral agents for chemophrophylaxis and therapy respiratory viral infections. Antiviral Res. 1985;(suppl 1):229–239
  27. Charoenvit Y, Brice GT, Bacon D, Majam V, Williams J, Abot E, et al. A small peptide (CEL-1000) derived from the beta-chain of the human major histocompatibility complex class II molecule induces complete protection against malaria in an antigen-independent manner. Antimicrob Agents Chemother. 2004;48:2455–2463
  28. Simbirtsev A, Kolobov A, Zabolotnych N, Pigareva N, Konusova V, Kotov A, et al. Biological activity of peptide SCV-07 against murine tuberculosis. Russ J Immunol. 2003;8:11–22
  29. Erlandsson H, Andersson U. The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 2004;34:103–112
  30. Yang H, Ochani M, Li J, Quiang X, Tanovic M, Harris HE, et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A. 2004;101:296–301
  31. Webster JI, Sternberg EM. Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products. J Endocrinol. 2004;181:207–221

 Supported by a Distinguished Research Professorship (Dr. Whelan), the Center for Technology, National Security Policy National Defense University; the Chad Baumann Research Fund Endowment (Dr Whelan); the Bleser Foundation Endowed Professorship (Dr Whelan); and Defense Advanced Research Projects Agency contract DAAH01-03-C-R120 (Drs Whelan and Amlie-Lefond).

PII: S0091-6749(05)01938-X

doi: 10.1016/j.jaci.2005.08.048

The Journal of Allergy and Clinical Immunology
Volume 116, Issue 6 , Pages 1334-1342 , December 2005

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