Influence of particle size on the pathology and efficacy of vaccination in a murine model of inhalational anthrax Free

Abstract

Deposition of endospores within either the lungs or nasal passages of A/J mice after aerosol exposure was influenced by different particle sized aerosols and resulted in different infection kinetics. The infection resulting from the inhalation of endospores within a 12 μm particle aerosol was prolonged compared to that from a 1 μm particle aerosol with a mean time-to-death of 161±16.1 h and 101.6±10.4 h, respectively. Inhalation of endospores within 1 μm or 12 μm particle aerosols resulted in a median lethal dose of 2432 and 7656 c.f.u., respectively. Initial involvement of the upper respiratory tract lymph nodes was observed in 75–83 % of mice exposed to either the 1 μm or 12 μm particle inhalational infections. Lung deposition was significantly greater after inhalation of the 1 μm particle aerosol with pronounced involvement of the mediastinal lymph node. Gastrointestinal involvement was observed only in mice exposed to 12 μm particle aerosols where bacteriological and histopathological analysis indicated primary gastritis (17 %), activation of the Peyer's patches (72 %) and colonization and necrosis of the mesenteric lymph nodes (67 %). Terminal disease was characterized by bacteraemia in both inhalational infections with preferential dissemination to spleen, liver, kidneys and thymus. Immunization with 1 μg recombinant protective antigen vaccine was equally efficacious against infections arising from the inhalation of 1 and 12 μm particle aerosols, providing 73–80 % survival under a suboptimum immunization schedule.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.024117-0
2010-12-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/59/12/1415.html?itemId=/content/journal/jmm/10.1099/jmm.0.024117-0&mimeType=html&fmt=ahah

References

  1. Beatty M. E., Ashford D. A., Griffin P. M., Tauxe R. V., Sobel J. 2003; Gastrointestinal anthrax: review of the literature. Arch Intern Med 163:2527–2531 [CrossRef]
    [Google Scholar]
  2. Butler T., Fu Y. S., Furman L., Almeida C., Almeida A. 1982; Experimental Yersinia pestis infection in rodents after intragastric inoculation and ingestion of bacteria. Infect Immun 36:1160–1167
    [Google Scholar]
  3. Cleret A., Quesnel-Hellmann A., Vallon-Eberhard A., Vernier B., Jung S., Vidal D., Mathieu J., Tournier J. N. 2007; Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route. J Immunol 178:7994–8001 [CrossRef]
    [Google Scholar]
  4. Day W. C., Berendt R. F. 1972; Experimental tularaemia in Macaca mulatta : relationship of aerosol particle size to the infectivity of airborne Pasteurella tularensis . Infect Immun 5:77–82
    [Google Scholar]
  5. Druett H. A., Henderson D. W., Packman L. P., Peacock S. 1953; Studies on respiratory infection. I. The influence of particle size on respiratory infection with anthrax spores. J Hyg (Lond 51:359–371 [CrossRef]
    [Google Scholar]
  6. Druett H. A., Robinson J. M., Henderson D. W., Packman L., Peacock S. 1956a; The influence of aerosol particle size on infection of the guinea-pig with Pasteurella pestis . J Hyg (Lond) 54:37–48 [CrossRef]
    [Google Scholar]
  7. Druett H. A., Henderson D. W., Peacock S. 1956b; Studies on respiratory infection. III. Experiments with Brucella suis . J Hyg (Lond 54:49–57 [CrossRef]
    [Google Scholar]
  8. Drysdale M., Heninger S., Hutt J., Chen Y., Lyons C. R., Koehler T. M. 2005; Capsule synthesis by Bacillus anthracis is required for dissemination in murine inhalation anthrax. EMBO J 24:221–227 [CrossRef]
    [Google Scholar]
  9. Duc L. H., Hong H. A., Fairweather N., Ricca E., Cutting S. M. 2003a; Bacterial spores as vaccine vehicles. Infect Immun 71:2810–2818 [CrossRef]
    [Google Scholar]
  10. Duc L. H., Hong H. A., Cutting S. M. 2003b; Germination of the spore in the gastrointestinal tract provides a novel route for heterologous antigen delivery. Vaccine 21:4215–4224 [CrossRef]
    [Google Scholar]
  11. Duncan S., Ho J. 2008; Estimation of viable spores in Bacillus atrophaeus (BG) particles of 1 to 9 μm size range. Clean Soil Air Water 36:584–592 [CrossRef]
    [Google Scholar]
  12. Duncan E. J. S., Kournikakis B., Ho J., Hill I. 2009; Pulmonary deposition of aerosolized Bacillus atrophaeus in a swine model due to exposure from a simulated anthrax letter incident. Inhal Toxicol 21:141–152 [CrossRef]
    [Google Scholar]
  13. Dunne P. J., Moran B., Cummins R. C., Mills K. H. G. 2009; CD11c+ CD8a+ dendritic cells promote protective immunity to respiratory infection with Bordetella pertussis . J Immunol 183:400–410 [CrossRef]
    [Google Scholar]
  14. Flick-Smith H. C., Eyles J. E., Hebdon R., Waters E. L., Beedham R. J., Stagg T. J., Miller J., Alpar H. O., Baillie L. W., Williamson E. D. 2002; Mucosal or parenteral administration of microsphere-associated Bacillus anthracis protective antigen protects against anthrax infection in mice. Infect Immun 70:2022–2028 [CrossRef]
    [Google Scholar]
  15. Flick-Smith H. C., Waters E. L., Walker N. J., Miller J., Stagg A. J., Green E. D., Williamson E. D. 2005; Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain. Microb Pathog 38:33–40 [CrossRef]
    [Google Scholar]
  16. Frankel A. E., Kuo S. R., Dostal D., Watson L., Duesbery N. S., Cheng C. P., Cheng H. J., Leppla S. H. 2009; Pathophysiology of anthrax. Front Biosci 14:4516–4524
    [Google Scholar]
  17. Fritz D. L., Jaax N. K., Lawrence W. B., Davis K. J., Pitt M. L., Ezzell J. W., Friedlander A. M. 1995; Pathology of experimental inhalation anthrax in the rhesus monkey. Lab Invest 73:691–702
    [Google Scholar]
  18. Fujimura Y., Takeda M., Ikai H., Haruma K., Akisada T., Harada T., Sakai T., Ohuchi M. 2004; The role of M cells of human nasopharyngeal lymphoid tissue in influenza virus sampling. Virchows Arch 444:36–42 [CrossRef]
    [Google Scholar]
  19. Glomski I. J., Corre J.-P., Mock M., Goossens P. L. 2007a; Nonencapsulated toxigenic Bacillus anthracis presents a specific growth and dissemination pattern in naïve and protective antigen-immune mice. Infect Immun 75:4754–4761 [CrossRef]
    [Google Scholar]
  20. Glomski I. J., Piris-Gimenez A., Huerre M., Mock M., Goossens P. L. 2007b; Primary involvement of pharynx and Peyer's patch in inhalational and intestinal anthrax. PLoS Pathog 3:e76 [CrossRef]
    [Google Scholar]
  21. Glomski I. J., Dumetz F., Jouvion G., Huerre M. R., Mock M., Goossens P. L. 2008; Inhaled non-capsulated Bacillus anthracis in A/J mice: nasopharynx and alveolar space as dual portals of entry, delayed dissemination, and specific organ targeting. Microbes Infect 10:1398–1404 [CrossRef]
    [Google Scholar]
  22. Goossens P. L. 2009; Animal models of human anthrax: the quest for the holy grail. Mol Aspects Med 30:467–480 [CrossRef]
    [Google Scholar]
  23. Gueirard P., Ave P., Balazuc A.-M., Thiberge S., Huerre M., Milon G., Guiso N. 2003; Bordetella bronchiseptica persists in the nasal cavities of mice and triggers early delivery of dendritic cells in the lymph nodes draining the lower and upper respiratory tract. Infect Immun 71:4137–4143 [CrossRef]
    [Google Scholar]
  24. Guyton A. C. 1947; Measurement of the respiratory volumes of laboratory animals. Am J Physiol 150:70–77
    [Google Scholar]
  25. Heine H. S., Bassett J., Miller L., Hartings J. M., Ivins B. E., Pitt M. L., Fritz D., Norris S. L., Byrne W. R. 2007; Determination of antibiotic efficacy against Bacillus anthracis in a mouse aerosol challenge model. Antimicrob Agents Chemother 51:1373–1379 [CrossRef]
    [Google Scholar]
  26. Holty J.-E. C., Bravat D. M., Liu H., Olshen R. A., McDonald K. M., Owens D. K. 2006a; Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med 144:270–280 [CrossRef]
    [Google Scholar]
  27. Holty J.-E. C., Kim R. Y., Bravata D. M. 2006b; Anthrax: a systematic review of atypical presentations. Ann Emerg Med 48:200–211 [CrossRef]
    [Google Scholar]
  28. Jahnsen F. L., Gran E., Haye R., Brandtzaeg P. 2004; Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes. Am J Respir Cell Mol Biol 30:31–37 [CrossRef]
    [Google Scholar]
  29. Jernigan D. B., Raghunathan P. L., Bell B. P., Brechner R., Bresnitz E. A., Butler J. C., Cetron M., Cohen M., Doyle T. other authors 2002; Investigation of bioterrorism-related anthrax, United States 2001: epidemiologic findings. Emerg Infect Dis 8:1019–1028 [CrossRef]
    [Google Scholar]
  30. Kang T. J., Basu S., Zhang L., Thomas K. E., Vogel S. N., Baillie L., Cross A. S. 2008; Bacillus anthracis spores and lethal toxin induce IL-1 β via functionally distinct signalling pathways. Eur J Immunol 38:1574–1584 [CrossRef]
    [Google Scholar]
  31. Kang T. J., Lee G. S., Kim S. K., Jin S. H., Chae G. T. 2010; Comparison of two mice strains, A/J and C57BL/6, in caspase-1 activity and IL-1 β secretion of macrophage to Mycobacterium leprae infection. Mediators Inflamm (in press
    [Google Scholar]
  32. Kwa S.-F., Beverley P., Smith A. L. 2006; Peyer's patches are required for the induction of rapid Th1 responses in the gut and mesenteric lymph nodes during an enteric infection. J Immunol 176:7533–7541 [CrossRef]
    [Google Scholar]
  33. Lever M. S., Stagg A. J., Nelson M., Pearce P., Stevens D. J., Scott A. M., Simpson A. J. H., Fulop M. J. 2008; Experimental respiratory anthrax infection in the common marmoset ( Callithrix jacchus . Int J Exp Pathol 89:171–179 [CrossRef]
    [Google Scholar]
  34. Loving C. L., Kennett M., Lee G. M., Grippe V. K., Merkel T. J. 2007; Murine aerosol challenge model of anthrax. Infect Immun 75:2689–2698 [CrossRef]
    [Google Scholar]
  35. Loving C. L., Khurana T., Osorio M., Lee G. M., Kelly V. K., Stibitz S., Merkel T. J. 2009; Role of anthrax toxins in dissemination, disease progression, and induction of protective adaptive immunity in the mouse aerosol challenge model. Infect Immun 77:255–265 [CrossRef]
    [Google Scholar]
  36. Lyons C. R., Lovchik J., Hutt J., Lipscomb M. F., Wang E., Heninger S., Berliba L., Garrison K. 2004; Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility. Infect Immun 72:4801–4809 [CrossRef]
    [Google Scholar]
  37. Macpherson A. J., Smith K. 2006; Mesenteric lymph nodes at the center of immune anatomy. J Exp Med 203:497–500 [CrossRef]
    [Google Scholar]
  38. Meyer M. A. 2003; Neurologic complications of anthrax. Arch Neurol 60:483–488 [CrossRef]
    [Google Scholar]
  39. Nicholson W. L., Farjado-Cavazos P., Rebeil R., Slieman T. A., Reisenman P. J., Law J. F., Xue Y. 2002; Bacterial endospores and their significance in stress resistance. Antonie van Leeuwenhoek 81:27–32 [CrossRef]
    [Google Scholar]
  40. Owen S. J., Batzloff M., Chehrehasa F., Meedeniya A., Casart Y., Logue C.-A., Hirst R. G., Peak I. R., Mackay-Sim A., Beacham I. R. 2009; Nasal-associated lymphoid tissue and olfactory epithelium as portals of entry for Burkholderia pseudomallei in murine melioidosis. J Infect Dis 199:1761–1770 [CrossRef]
    [Google Scholar]
  41. Park H.-S., Francis K. P., Yu J., Cleary P. P. 2003; Membranous cells in nasal-associated lymphoid tissue: a portal of entry for the respiratory mucosal pathogen group A streptococcus. J Immunol 171:2532–2537 [CrossRef]
    [Google Scholar]
  42. Passalacqua K. D., Bergman N. H. 2006; Bacillus anthracis : interactions with the host and establishment of inhalational anthrax. Future Microbiol 1:397–415 [CrossRef]
    [Google Scholar]
  43. Redmond C., Baillie L. W. J., Hibbs S., Moir A. J. G., Moir A. 2004; Identification of proteins in the exosporium of Bacillus anthracis . Microbiology 150:355–363 [CrossRef]
    [Google Scholar]
  44. Reed L. J., Muench H. 1938; A simple method of estimating fifty per cent endpoints. Am J Hyg 27:493–497
    [Google Scholar]
  45. Roy C. J., Hale M., Hartings J. M., Pitt L., Duniho S. 2003; Impact of inhalation exposure modality and particle size on the respiratory deposition of ricin in Balb/c mice. Inhal Toxicol 15:619–638 [CrossRef]
    [Google Scholar]
  46. Sanz P., Teel L. D., Alem F., Carvalho H. M., Darnell S. C., O'Brien A. D. 2008; Detection of Bacillus anthracis spore germination in vivo by bioluminescence imaging. Infect Immun 76:1036–1047 [CrossRef]
    [Google Scholar]
  47. Setlow P. 2006; Spores of Bacillus subtilis : their resistance to and killing by radiation, heat and chemicals. J Appl Microbiol 101:514–525 [CrossRef]
    [Google Scholar]
  48. Stokes M. G. M., Titball R. W., Neeson B. N., Galen J. E., Walker N. J., Stagg A. J., Jenner D. C., Thwaite J. E., Nataro J. P. other authors 2007; Oral administration of a Salmonella enterica -based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis . Infect Immun 75:1827–1834 [CrossRef]
    [Google Scholar]
  49. Tam M. A., Rydström A., Sundquist M., Wick M. J. 2008; Early cellular responses to Salmonella infection: dendritic cells, monocytes, and more. Immunol Rev 225:140–162 [CrossRef]
    [Google Scholar]
  50. Thomas R. J., Webber D., Sellors W., Collinge A., Frost A., Stagg A. J., Bailey S. C., Jayasekera P. N., Taylor R. R. other authors 2008; Characterisation and deposition of respirable large and small particle bioaerosols. Appl Environ Microbiol 74:6437–6443 [CrossRef]
    [Google Scholar]
  51. Thomas R. J., Webber D., Collinge A., Stagg A. J., Bailey S. C., Nunez A., Gates A., Jayasekera P. N., Taylor R. R. other authors 2009; Different pathologies but equal levels of responsiveness to the recombinant F1 and V antigen vaccine and ciprofloxacin in a murine model of plague caused by small- and large-particle aerosols. Infect Immun 77:1315–1323 [CrossRef]
    [Google Scholar]
  52. Todd S. J., Moir A. J. G., Johnson M. J., Moir A. 2003; Genes of Bacillus cereus and Bacillus anthracis encoding proteins of the exosporium. J Bacteriol 185:3373–3378 [CrossRef]
    [Google Scholar]
  53. Tutrone W. D., Scheinfeld N. S., Weinberg J. M. 2002; Cutaneous anthrax: a concise review. Cutis 69:27–33
    [Google Scholar]
  54. Twenhafel N. A., Leffel E., Pitt M. L. M. 2007; Pathology of inhalational anthrax infection in the African Green monkey. Vet Pathol 44:716–721 [CrossRef]
    [Google Scholar]
  55. Van den Broeck W., Derore A., Simeons P. 2006; Anatomy and nomenclature of murine lymph nodes: descriptive study and nomenclatory standardization in BALB/cAnNCrl mice. J Immunol Methods 312:12–19 [CrossRef]
    [Google Scholar]
  56. Vasconcelos D., Barnewall R., Babin M., Hunt R., Estep J., Nielsen C., Carnes R., Carney J. 2003; Pathology of inhalation anthrax in cynomolgus monkeys ( Macaca fascicularis . Lab Invest 83:1201–1209 [CrossRef]
    [Google Scholar]
  57. Welkos S. L., Keener T. J., Gibbs P. H. 1986; Differences in susceptibility of inbred mice to Bacillus anthracis . Infect Immun 51:795–800
    [Google Scholar]
  58. Williamson E. D., Hodgson I., Walker N. J., Topping A. W., Duchars M. G., Mott J. M., Estep J., LeButt C., Flick-Smith H. C. other authors 2005; Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax. Infect Immun 73:5978–5987 [CrossRef]
    [Google Scholar]
  59. Zaucha G. M., Pitt L. M., Estep J., Ivins B. E., Friedlander A. M. 1998; The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation. Arch Pathol Lab Med 122:982–992
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.024117-0
Loading
/content/journal/jmm/10.1099/jmm.0.024117-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed