1887

Microbiology Society logo

Volume 154, Issue 7

Induction of innate immunity by lipid A mimetics increases survival from pneumonic plague Free

Abstract

This study analysed the effect of priming the innate immune system using synthetic lipid A mimetics in a murine pulmonary infection model. Two aminoalkyl glucosaminide 4-phosphate (AGP) Toll-like receptor 4 (TLR4) ligands, delivered intranasally, extended time to death or protected against a lethal CO92 challenge. The level of protection was dependent upon the challenge dose of and the timing of AGP therapy. Protection correlated with cytokine induction and a decreased bacterial burden in lung tissue. AGP protection was TLR4-dependent and was not evidenced in transgenic TLR4-deficient mice. AGP therapy augmented with subtherapeutic doses of gentamicin produced dramatically enhanced survival. Combined, these results indicated that AGPs may be useful in protection of immunologically naive individuals against plague and potentially other infectious agents, and that AGP therapy may be used synergistically with other therapies.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): AGP, aminoalkyl glucosaminide 4-phosphate , i.n., intranasal(ly) , i.p., intraperitoneal(ly) , IFN-γ, interferon-γ , IL, interleukin , PAMP, pathogen-associated molecular pattern , TLR, Toll-like receptor , TNF-α, tumour necrosis factor-α and TTD, time to death
SGM
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2008/017566-0
2008-07-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/micro/154/7/2131.html?itemId=/content/journal/micro/10.1099/mic.0.2008/017566-0&mimeType=html&fmt=ahah

References

  1. Anderson G. W. Jr, Leary S. E. C., Williamson E. D., Titball R. W., Welkos S. L., Worsham P. L., Friedlander A. M. 1996; Recombinant V antigen protects mice against pneumonic plague and bubonic plague caused by F1-capsule positive and -negative strains of Yersinia pestis. Infect Immun 64:4580–4585
     [Google Scholar]
  2. Andrews G. P., Heath D. G., Anderson G. W. Jr, Welkos S. L., Friedlander A. M. 1996; Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge. Infect Immun 64:2180–2187
     [Google Scholar]
  3. Brubaker R. R. 2003; Interleukin-10 and inhibition of innate immunity to yersiniae: roles of Yops and LcrV (V-antigen. Infect Immun 71:3673–3681
     [Google Scholar]
  4. Bruneteau M., Minka S. 2003; Lipopolysaccharides of bacterial pathogens from the genus Yersinia: a mini-review. Biochimie 85:145–152
     [Google Scholar]
  5. Byrne W. R., Welkos S. L., Pitt M. L., Davis K. J., Brueckner R. P., Ezzell J. W., Nelson G. O., Vaccaro J. R., Battersby L. C., Friedlander A. M. 1998; Antibiotic treatment of experimental pneumonic plague in mice. Antimicrob Agents Chemother 42:675–681
     [Google Scholar]
  6. Cluff C. W., Baldridge J. R., Stover A. G., Evans J. T., Johnson D. A., Lacy M. J., Clawson V. G., Yorgensen V. M., Johnson C. L. other authors 2005; Synthetic Toll-like receptor 4 agonists stimulate innate resistance to infectious challenge. Infect Immun 73:3044–3052
     [Google Scholar]
  7. Flondor M., Hofstetter C., Boost K. A., Betz C., Homann M., Zwissler B. 2007; Isoflurane inhalation after induction of endotoxemia in rats attenuates the systemic cytokine response. Eur Surg Res 40:1–6
     [Google Scholar]
  8. Frean J., Klugman K. P., Arntzen L., Bukofzer S. 2003; Susceptibility of Yersinia pestis to novel and conventional antimicrobial agents. J Antimicrob Chemother 52:294–296
     [Google Scholar]
  9. Guthrie L. A., McPhail L. C., Henson P. M., Hohnston R. B. 1984; Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipolysaccharide. Evidence for increased activity of the superoxide-producing enzyme. J Exp Med 160:1656–1671
     [Google Scholar]
  10. Heine H. S., Louie A., Sorgel F., Bassett J., Miller L., Sullivan L. J., Kinzig-Schippers M., Drusano G. L. 2007; Comparison of 2 antibiotics that inhibit protein synthesis for the treatment of infection with Yersinia pestis delivered by aerosol in a mouse model of pneumonic plague. J Infect Dis 196:782–787
     [Google Scholar]
  11. Honko A. N., Mizel S. B. 2004; Mucosal administration of flagellin induces innate immunity in the mouse lung. Infect Immun 72:6676–6679
     [Google Scholar]
  12. Inglesby T. V., Dennis D. T., Henderson D. A., Bartlett J. G., Ascher M. S., Eitzen E., Fine A. D., Friedlander A. M. Jr, Hauer J. other authors 2000; Plague as a biological weapon: medical and public health management. JAMA 283:2281–2290
     [Google Scholar]
  13. Kaufman S. H. E., Medzhitov R., Gordon S. 2004 The Innate Immune Response to Infection Washington, DC: American Society for Microbiology;
  14. Lathem W. W., Crosby S. D., Miller V. L., Goldman W. E. 2005; Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity. Proc Natl Acad Sci U S A 102:17786–17791
     [Google Scholar]
  15. Lathem W. W., Price P. A., Miller V. L., Goldman W. E. 2007; A plasminogen-activating protease specifically controls the development of primary pneumonic plague. Science 315:509–513
     [Google Scholar]
  16. Leary S. E., Griffin K. F., Garmory H. S., Williamson E. D., Titball R. W. 1997; Expression of an F1/V fusion protein in attenuated Salmonella typhimurium and protection of mice against plague. Microb Pathog 23:167–179
     [Google Scholar]
  17. Martin M., Michalek S. M., Katz J. 2003; Role of innate immune factors in the adjuvant activity of monophosphoryl lipid A. Infect Immun 71:2498–2507
     [Google Scholar]
  18. Minnich S. A., Rohde H. N. 2007; A rationale for repression and/or loss of motility by pathogenic Yersinia in the mammalian host. Adv Exp Med Biol 603:298–310
     [Google Scholar]
  19. Montminy S. W., Khan N., McGrath S., Malkowicz M. J., Sharp F., Conlan J. E., Fukase K., Kusumoto S., Sweet C. other authors 2006; Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response. Nat Immunol 7:1066–1073
     [Google Scholar]
  20. Mukhopadhyay S., Herre J., Brown G. D., Gordon S. 2004; The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology 112:521–530
     [Google Scholar]
  21. Overheim K. A., DePaolo R. W., DeBord K. L., Morrin E. M., Anderson D. M., Green N. M., Brubaker R. R., Jabri B., Schneewind O. 2005; LcrV plague vaccine with altered immunomodulatory properties. Infect Immun 73:5152–5159
     [Google Scholar]
  22. Pammit M. A., Budhavarapu V. N., Raulie E. K., Klose K. E., Teale J. M., Arulanandam B. P. 2004; Intranasal interleukin-12 treatment promotes antimicrobial clearance and survival in pulmonary Francisella tularensis subsp. novicida infection. Antimicrob Agents Chemother 48:4513–4519
     [Google Scholar]
  23. Parent M. A., Wilhelm L. B., Kummer L. W., Szaba F. M., Mullarky I. K., Smiley S. T. 2006; Gamma interferon, tumor necrosis factor alpha, and nitric oxide synthase 2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Yersinia pestis infection. Infect Immun 74:3381–3386
     [Google Scholar]
  24. Perry R. D., Fetherston J. D. 1997; Yersinia pestis – etiological agent of plague. Clin Microbiol Rev 10:35–66
     [Google Scholar]
  25. Philipovskiy A. V., Cowan C., Wulff-Strobel C. R., Burnett S. H., Kerschen E. J., Cohen D. A., Kaplan A. M., Straley S. C. 2005; Antibody against V-antigen prevents Yop-dependent growth of Yersinia pestis. Infect Immun 73:1532–1542
     [Google Scholar]
  26. Pouliot K., Pan N., Wang S., Lu S., Lien E., Goguen J. D. 2007; Evaluation of the role of LcrV-Toll-like receptor 2-mediated immunomodulation in the virulence of Yersinia pestis. Infect Immun 75:3571–3580
     [Google Scholar]
  27. Raetz C. R., Whitfield C. 2002; Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700
     [Google Scholar]
  28. Rebeil R., Ernst R. K., Gowen B. B., Miller S. I., Hinnebusch B. J. 2004; Variation in lipid A structure in the pathogenic yersiniae. Mol Microbiol 52:1363–1373
     [Google Scholar]
  29. Roy C. R., Mocarski E. S. 2007; Pathogen subversion of cell-intrinsic innate immunity. Nat Immunol 8:1179–1187
     [Google Scholar]
  30. Russell P., Eley S. M., Hibbs S. E., Manchee R. J., Stagg A. J., Titball R. W. 1995; A comparison of plague vaccine USP and EV76 vaccine induced protection against Yersinia pestis in a murine model. Vaccine 13:1551–1556
     [Google Scholar]
  31. Sheppard F. R., Kelher M. R., Moore E. E., McLaughlin N. J., Banerjee A., Silliman C. C. 2005; Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation. J Leukoc Biol 78:1025–1042
     [Google Scholar]
  32. Sweet C. R., Conlon J., Golenbock D. T., Goguen J., Silverman N. 2007; YopJ targets TRAF proteins to inhibit TLR-mediated NF- κB, MAPK, and IRF3 signal transduction. Cell Microbiol 9:2700–2715
     [Google Scholar]
  33. Viboud G. I., Bliska J. B. 2005; Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 59:69–89
     [Google Scholar]
  34. Viboud G. I., So S. S., Ryndak M. B., Bliska J. B. 2003; Proinflammatory signaling stimulated by the type III translocation factor YopB is counteracted by multiple effectors in epithelial cells infected with Yersinia pseudotuberculosis. Mol Microbiol 47:1305–1315
     [Google Scholar]
  35. Williamson E. D., Eley S. M., Stagg A. J., Green M., Russell P., Titball R. W. 2000; A single dose sub-unit vaccine protects against pneumonic plague. Vaccine 19:566–571
     [Google Scholar]
  36. Williamson E. D., Stagg A. J., Eley S. M., Taylor R., Green M., Jones S. M., Titball R. W. 2007; Kinetics of the immune response to the (F1+V) vaccine in models of bubonic and pneumonic plague. Vaccine 25:1142–1148
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2008/017566-0
Loading
Induction of innate immunity by lipid A mimetics increases survival from pneumonic plague
Microbiology 154, 2131 (2008); https://doi.org/10.1099/mic.0.2008/017566-0
/content/journal/micro/10.1099/mic.0.2008/017566-0
/content/journal/micro/10.1099/mic.0.2008/017566-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error