1887

Abstract

The contribution of reactive oxygen species produced by neutrophils against infection is not widely recognized. Myeloperoxidase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from HO. This study investigated the role of MPO in immunological defence against in an MPO-deficient (MPO) mouse model. The survival of MPO mice infected either intranasally or intravenously with was lower than that of identically challenged wild-type mice. The MPO mice that received intranasal injection of had significantly larger lung fungal burdens than wild-type mice. On day 7, MPO mice had a significantly higher lung concentration of interleukin (IL)-4 and lower concentrations of IL-2, IL-12p70 and interferon (IFN)- than wild-type mice, suggesting a weak Th1 response in the MPO mice to . Pathologically, the MPO mice with intranasal infection showed more severe pneumonia than wild-type mice, which was associated with an increase in the levels of IL-1/ in the lungs. In addition, in MPO mice, the pulmonary infection disseminated to the brain with occasional meningitis. The keratinocyte-derived cytokine (KC) level in the brain of infected MPO mice was higher than that of control mice. Both intranasal and intravenous infections resulted in a higher number of fungi in the spleen of MPO mice compared to wild-type, suggesting decreased resistance to not only in the lungs but also in the spleen in the absence of MPO. Taken together, these data suggest a major role of MPO in the response to cryptococcal infection.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.46620-0
2006-09-01
2020-05-27
Loading full text...

Full text loading...

/deliver/fulltext/jmm/55/9/1291.html?itemId=/content/journal/jmm/10.1099/jmm.0.46620-0&mimeType=html&fmt=ahah

References

  1. Aratani Y., Koyama H., Nyui S., Suzuki K., Kura F., Maeda N. 1999; Severe impairment in early host defense against Candida albicans in mice deficient in myeloperoxidase. Infect Immun 67:1828–1836
    [Google Scholar]
  2. Aratani Y., Kura F., Watanabe H., Akagawa H., Takano Y., Suzuki K., Maeda N., Koyama H. 2000; Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase. J Infect Dis 182:1276–1279 [CrossRef]
    [Google Scholar]
  3. Aratani Y., Kura F., Watanabe H., Akagawa H., Takano Y., Suzuki K., Dinauer M. C., Maeda N., Koyama H. 2002a; Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans . J Infect Dis 185:1833–1837 [CrossRef]
    [Google Scholar]
  4. Aratani Y., Kura F., Watanabe H., Akagawa H., Takano Y., Suzuki K., Dinauer M. C., Maeda N., Koyama H. 2002b; Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus . Med Mycol 40:557–563 [CrossRef]
    [Google Scholar]
  5. Bell M. D., Taub D. D., Perry V. H. 1996; Overriding the brain's intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines. Neuroscience 74:283–292 [CrossRef]
    [Google Scholar]
  6. Buchanan K. L., Doyle H. A. 2000; Requirement for CD4+ T lymphocytes in host resistance against Cryptococcus neoformans in the central nervous system of immunized mice. Infect Immun 68:456–462 [CrossRef]
    [Google Scholar]
  7. Chatelain R., Varkila K., Coffman R. L. 1992; IL-4 induces a Th2 response in Leishmania major -infected mice. J Immunol 148:1182–1187
    [Google Scholar]
  8. Chuck S. L., Sande M. A. 1989; Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 321:794–799 [CrossRef]
    [Google Scholar]
  9. Decken K., Kohler G., Palmer-Lehmann K., Wunderlin A., Mattner F., Magram J., Gately M. K., Alber G. 1998; Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans . Infect Immun 66:4994–5000
    [Google Scholar]
  10. Diamond R. D., Clark R. A., Haudenschild C. C. 1980; Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. J Clin Invest 66:908–917 [CrossRef]
    [Google Scholar]
  11. Eisenhauer P. B., Lehrer R. I. 1992; Mouse neutrophils lack defensins. Infect Immun 60:3446–3447
    [Google Scholar]
  12. Graybill J. R., Bocanegra R., Lambros C., Luther M. F. 1997; Granulocyte colony stimulating factor therapy of experimental cryptococcal meningitis. J Med Vet Mycol 35:243–247 [CrossRef]
    [Google Scholar]
  13. Hansson M., Olsson I., Nauseef W. M. 2006; Biosynthesis, processing, and sorting of human myeloperoxidase. Arch Biochem Biophys 445:214–224 [CrossRef]
    [Google Scholar]
  14. Hoag K. A., Lipscomb M. F., Izzo A. A., Street N. E. 1997; IL-12 and IFN-gamma are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 mice. Am J Respir Cell Mol Biol 17:733–739 [CrossRef]
    [Google Scholar]
  15. Kawakami K., Tohyama M., Teruya K., Kudeken N., Xie Q., Saito A. 1996; Contribution of interferon-gamma in protecting mice during pulmonary and disseminated infection with Cryptococcus neoformans . FEMS Immunol Med Microbiol 13:123–130
    [Google Scholar]
  16. Klebanoff S. J. 2005; Myeloperoxidase: friend and foe. J Leukoc Biol 77:598–625 [CrossRef]
    [Google Scholar]
  17. Komatsu S., Flores S., Gerritsen M. E., Anderson D. C., Granger D. N. 1997; Differential up-regulation of circulating soluble and endothelial cell intercellular adhesion molecule-1 in mice. Am J Pathol 151:205–214
    [Google Scholar]
  18. Kozel T. R. 1993; Cryptococcosis. In Fungal Infections and Immune Responses pp  277–302 Edited by Murphy J. W., Friedman H., Bendinelli M. New York: Plenum;
    [Google Scholar]
  19. Lappalainen U., Whitsett J. A., Wert S. E., Tichelaar J. W., Bry K. 2005; Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 32:311–318 [CrossRef]
    [Google Scholar]
  20. Leal L. M., Moss D. W., Kuhn R., Muller W., Liew F. Y. 1993; Interleukin-4 transgenic mice of resistant background are susceptible to Leishmania major infection. Eur J Immunol 23:566–569 [CrossRef]
    [Google Scholar]
  21. Lee S. C., Dickson D. W., Casadevall A. 1996; Pathology of cryptococcal meningoencephalitis: analysis of 27 patients with pathogenetic implications. Hum Pathol 27:839–847 [CrossRef]
    [Google Scholar]
  22. Lehrer R. I., Cline M. J. 1969; Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J Clin Invest 48:1478–1488 [CrossRef]
    [Google Scholar]
  23. Lipovsky M. M., Gekker G., Hu S., Ehrlich L. C., Hoepelman A. I., Peterson P. K. 1998; Cryptococcal glucuronoxylomannan induces interleukin (IL)-8 production by human microglia but inhibits neutrophil migration toward IL-8. J Infect Dis 177:260–263 [CrossRef]
    [Google Scholar]
  24. Lovchik J., Lipscomb M., Lyons C. R. 1997; Expression of lung inducible nitric oxide synthase protein does not correlate with nitric oxide production in vivo in a pulmonary immune response against Cryptococcus neoformans . J Immunol 158:1772–1778
    [Google Scholar]
  25. Mambula S. S., Simons E. R., Hastey R., Selsted M. E., Levitz S. M. 2000; Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans . Infect Immun 68:6257–6264 [CrossRef]
    [Google Scholar]
  26. Mednick A. J., Feldmesser M., Rivera J., Casadevall A. 2003; Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis. Eur J Immunol 33:1744–1753 [CrossRef]
    [Google Scholar]
  27. Miller M. F., Mitchell T. G. 1991; Killing of Cryptococcus neoformans strains by human neutrophils and monocytes. Infect Immun 59:24–28
    [Google Scholar]
  28. Murphy J. W. 1996; Cell-mediated immunity. In The Mycota vol 7 pp  67–97 Edited by Miller J. D., Howard D. H. New York: Springer;
    [Google Scholar]
  29. Nauseef W. M. 1998; Insights into myeloperoxidase biosynthesis from its inherited deficiency. J Mol Med 76:661–668 [CrossRef]
    [Google Scholar]
  30. Nunoi H., Kohi F., Kajiwara H., Suzuki K. 2003; Prevalence of inherited myeloperoxidase deficiency in Japan. Microbiol Immunol 47:527–531 [CrossRef]
    [Google Scholar]
  31. Parry M. F., Root R. K., Metcalf J. A., Delaney K. K., Kaplow L. S., Richar W. J. 1981; Myeloperoxidase deficiency: prevalence and clinical significance. Ann Intern Med 95:293–301 [CrossRef]
    [Google Scholar]
  32. Retini C., Vecchiarelli A., Monari C., Tascini C., Bistoni F., Kozel T. R. 1996; Capsular polysaccharide of Cryptococcus neoformans induces proinflammatory cytokine release by human neutrophils. Infect Immun 64:2897–2903
    [Google Scholar]
  33. Schleimer R. P., Rutledge B. K. 1986; Cultured human vascular endothelial cells acquire adhesiveness for neutrophils after stimulation with interleukin 1, endotoxin, and tumor-promoting phorbol diesters. J Immunol 136:649–654
    [Google Scholar]
  34. Scholz D., Devaux B., Hirche A., Potzsch B., Kropp B., Schaper W., Schaper J. 1996; Expression of adhesion molecules is specific and time-dependent in cytokine-stimulated endothelial cells in culture. Cell Tissue Res 284:415–423 [CrossRef]
    [Google Scholar]
  35. Tateda K., Moore T. A., Deng J. C., Newstead M. W., Zeng X., Matsukawa A., Swanson M. S., Yamaguchi K., Standiford T. J. 2001; Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. J Immunol 166:3355–3361 [CrossRef]
    [Google Scholar]
  36. Ulich T. R., Watson L. R., Yin S. M., Guo K. Z., Wang P., Thang H., del Castillo J. 1991; The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate. Am J Pathol 138:1485–1496
    [Google Scholar]
  37. Vecchiarelli A., Retini C., Casadevall A., Monari C., Pietrella D., Kozel T. R. 1998; Involvement of C3a and C5a in interleukin-8 secretion by human polymorphonuclear cells in response to capsular material of Cryptococcus neoformans . Infect Immun 66:4324–4330
    [Google Scholar]
  38. Wagner J. G., Roth R. A. 2000; Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol Rev 52:349–374
    [Google Scholar]
  39. Yang H. M., Ma J. Y., Castranova V., Ma J. K. 1997; Effects of diesel exhaust particles on the release of interleukin-1 and tumor necrosis factor-alpha from rat alveolar macrophages. Exp Lung Res 23:269–284 [CrossRef]
    [Google Scholar]
  40. Yuan R. R., Casadevall A., Oh J., Scharff M. D. 1997; T cells cooperate with passive antibody to modify Cryptococcus neoformans infection in mice. Proc Natl Acad Sci U S A 94:2483–2488 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.46620-0
Loading
/content/journal/jmm/10.1099/jmm.0.46620-0
Loading

Data & Media loading...

Most cited this month 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