Mycopathologia

, Volume 109, Issue 2, pp 99–109 | Cite as

Experimental pulmonary candidiasis

  • Richard T. Sawyer
Article

Abstract

The initial interaction of Candida albicans with pulmonary tissue of B6D2/F1 mice was investigated. The LD50 for mice challenged intravenously (IV) was approximately 3 × 105 yeasts, whereas the LD50 by the intratracheal (IT) route was in excess of 108 yeasts. Mice challenged IV died of progressive yeast growth in the kidneys. In contrast, mice challenged IT rapidly eliminated the entire inoculum by the first day after challenge. Resident pulmonary alveolar macrophages (PAM) killed upwards of 70% of C. albicans in an in vitro killing assay. At effector: target ratios favoring the effector cell population resident PAM were able to restrict the formation of yeast germ tubes to only 30% of the yeasts, whereas at equivalent ratios virtually all of the intracellular yeasts produced germ tubes. Evaluation of the ability of PAM, harvested from genetically different strains of inbred mice, to kill C. albicans in vitro showed that killing ability was a property of resident PAM from mice with the black 6 background. It was discovered that during the initial stages of infection in vivo, the expression of the F4/80 surface molecule was down regulated, and the expression of the Mac 1 surface molecule upregulated. There were no quantitative changes in expression of either Mac 2, Mac 3, Ly 5 or the 5C6 surface epitopes. Taken together, the data show that pulmonary tissue is quantitatively very resistant to C. albicans infection, because of the ability of resident PAM to rapidly phagocytize and kill yeasts. Killing of C. albicans by resident PAM may be a property of a subset of this mononuclear phagocyte population and was accompanied by alterations in the expression of surface molecules.

Key words

Candida albicans pulmonary alveolar macrophage host-parasite interaction pulmonary infection phagocytosis and killing 

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References

  1. 1.
    Alan R, Ezekowitz B, Gordon S. Alterations of surface properties by macrophage activation: Expression of receptors for Fc and mannose-terminal glycoproteins and differentiation antigens. Contemp Topics Immunobiol. 1984; 13, 33.Google Scholar
  2. 2.
    Baum GL. The significance of Candida albicans in human sputum. New Eng J Med 1960; 263, 70.Google Scholar
  3. 3.
    Brummer E, Morrison CJ, Stevens DA. Recombinant and natural gamma-interferon activation of macrophages in vitro: Different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi. Infect Immun 1985; 49, 724.Google Scholar
  4. 4.
    Brummer E, Stevens DA. Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines. Clin exp Immunol 1987; 70, 520.Google Scholar
  5. 5.
    Danley DL, Polakoff J. Rapid killing of monocytes in vitro by Candida albicans yeast cells. Infect Immun 1986; 51, 307.Google Scholar
  6. 6.
    Dethloff LA, Lehnert BE. Pulmonary interstitial macrophages: Isolation and flow cytometric comparisons with alveolar macrophages and blood monocytes. J Leuk Biol 1988; 43, 80.Google Scholar
  7. 7.
    Hayes CE, Klyczek KK, Krum DP, Whitcomb RM, Hullett D, Cantor H. Chromosome 4 Jt gene controls murine T cell surface I-J expression. Science 1984; 223, 559.Google Scholar
  8. 8.
    Holt PG. Alveolar macrophage I. A simple technique for the preparation of high numbers of viable alveolar macrophage from small laboratory animals. J Immunol Meth 1979; 27, 189.Google Scholar
  9. 9.
    Hector RF, Domer JE, Carrow EW. Immune responses to Candida albicans in genetically distinct mice. Infect Immun 1982; 38, 1020.Google Scholar
  10. 10.
    Kruzinger K, Reynolds T, Germain R, Davignon D, Martz E, Springer TA. A novel lymphocyte function associated antigen (LFA-1): Cellular distribution, quantitative expression, and structure. J Immunol 1981; 127, 596.Google Scholar
  11. 11.
    Lee SH, Starkey PM, Gordon S. Quantitative analysis of total macrophage content in adult mouse tissues: Immunochemical studies with monoclonal antibody F4/80. J Exp Med 1985; 161, 475.Google Scholar
  12. 12.
    Lehrer RI, Ferrari LG, Delafield JP, Sorrell T. Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans. Infect Immun 1980; 28, 1001.Google Scholar
  13. 13.
    Leunk RD, Moon RJ. Physiological and metabolic alterations accompanying systemic candidiasis in mice. Infect Immun 1979; 26, 1035.Google Scholar
  14. 14.
    Maiti PK, Kumar R, Monapatra LN. Candidacidal activity of mouse macrophages in vitro. Infect Immun 1980; 29, 477.Google Scholar
  15. 15.
    Myerowitz RL, Pazin GJ, Allen CM. Disseminated candidiasis: Changes in incidence, underlying disease, and pathology. Am J Clin Pathol 1977; 68, 29.Google Scholar
  16. 16.
    Nugent KM, Onofrio JM. Pulmonary tissue resistance to Candida albicans in normal and immunosuppressed mice. Am Rev Respir Dis 1983; 128, 909.Google Scholar
  17. 17.
    Oghiso Y. Morphologic and functional heterogeneity among rat alveolar macrophage fractions isolated by centrifugation on density gradients. J Leuk Biol 1987;42, 188.Google Scholar
  18. 18.
    Rosen H, Gordon S. Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. J Exp Med 1987; 166, 1685.Google Scholar
  19. 19.
    Sasada M, Johnston RB, Jr. Macrophage microbicidal activity: correlation between phagocytosis-associated oxidative metabolism and killing of Candida by macrophages. J Exp Med 1980; 152, 85.Google Scholar
  20. 20.
    Sawyer RT, Strausbauch PH, Volkman A. Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89. Lab Invest 1982; 46, 165.Google Scholar
  21. 21.
    Sawyer RT. The significance of local resident pulmonary alveolar macrophage proliferation to population renewal. J Leuk Biol 1986; 39, 77.Google Scholar
  22. 22.
    Sawyer RT. The cytokinetic behavior of pulmonary alveolar macrophages in monocytopenic mice. J Leuk Biol 1986; 39, 89.Google Scholar
  23. 23.
    Springer TA, Unkeless JC. Analysis of macrophage differentiation and function with monoclonal antibodies. Contemp Topics Immunobiol 1984, 13, 1.Google Scholar
  24. 24.
    Tarling JD, Lin HS, Hsu S. Self-renewal of pulmonary alveolar macrophages: Evidence from radiation chimera studies. J Leuk Biol 1987; 42, 443.Google Scholar
  25. 25.
    Volkman A, Gowans JL. The production of macrophages in the rat. Brit J Exp Pathol 1965; 46, 50.Google Scholar
  26. 26.
    Volkman A, Gowans JL. The origin of macrophages from bone marrow in the rat. Brit J Exp Pathol 1965;46, 62.Google Scholar
  27. 27.
    Volkman A. Disparity in the origin of mononuclear phagocyte populations. J Reticuloendothel Soc 1976; 19, 249.Google Scholar
  28. 28.
    Wilcoxon F & Wilcox RA. Some rapid approximate statistical procedures. New York: American Cyanamide Co., 1949.Google Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • Richard T. Sawyer
    • 1
  1. 1.The Trudeau InstituteSaranac LakeUSA

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