Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Sep;63(9):3360–3366. doi: 10.1128/iai.63.9.3360-3366.1995

Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells.

S Schelenz 1, R Malhotra 1, R B Sim 1, U Holmskov 1, G J Bancroft 1
PMCID: PMC173462  PMID: 7642263

Abstract

Cryptococcus neoformans is an opportunistic pathogen in AIDS patients causing disseminated disease and lethal meningitis after inhalation of acapsular or sparsely encapsulated yeast cells. In this study we have investigated whether a recently described family of primitive opsonins, termed collectins, contribute to innate resistance against C. neoformans. The pulmonary surfactant proteins SP-A and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound in a calcium-dependent manner to acapsular C. neoformans in vitro. Binding was concentration dependent and abolished by competition with defined mono- and oligosaccharides. In contrast, no binding of the collectins was observed with the encapsulated form of the yeast. Furthermore, binding of purified collectin SP-D, but not SP-A, mannose-binding protein, or CL-43, led to a concentration-dependent agglutination of acapsular C. neoformans. These data indicate that collectins recognize carbohydrate structures in the cell wall of an initial infectious form of C. neoformans and may play a role in early antifungal defenses in the lung.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bhattacharjee A. K., Bennett J. E., Glaudemans C. P. Capsular polysaccharides of Cryptococcus neoformans. Rev Infect Dis. 1984 Sep-Oct;6(5):619–624. doi: 10.1093/clinids/6.5.619. [DOI] [PubMed] [Google Scholar]
  2. Collins H. L., Bancroft G. J. Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans. Eur J Immunol. 1992 Jun;22(6):1447–1454. doi: 10.1002/eji.1830220617. [DOI] [PubMed] [Google Scholar]
  3. Cross C. E., Bancroft G. J. Ingestion of acapsular Cryptococcus neoformans occurs via mannose and beta-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form. Infect Immun. 1995 Jul;63(7):2604–2611. doi: 10.1128/iai.63.7.2604-2611.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crouch E., Parghi D., Kuan S. F., Persson A. Surfactant protein D: subcellular localization in nonciliated bronchiolar epithelial cells. Am J Physiol. 1992 Jul;263(1 Pt 1):L60–L66. doi: 10.1152/ajplung.1992.263.1.L60. [DOI] [PubMed] [Google Scholar]
  5. Ezekowitz R. A., Kuhlman M., Groopman J. E., Byrn R. A. A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. J Exp Med. 1989 Jan 1;169(1):185–196. doi: 10.1084/jem.169.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Farhi F., Bulmer G. S., Tacker J. R. Cryptococcus neoformans IV. The Not-So-Encapsulated Yeast. Infect Immun. 1970 Jun;1(6):526–531. doi: 10.1128/iai.1.6.526-531.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Geertsma M. F., Nibbering P. H., Haagsman H. P., Daha M. R., van Furth R. Binding of surfactant protein A to C1q receptors mediates phagocytosis of Staphylococcus aureus by monocytes. Am J Physiol. 1994 Nov;267(5 Pt 1):L578–L584. doi: 10.1152/ajplung.1994.267.5.L578. [DOI] [PubMed] [Google Scholar]
  8. Geertsma M. F., Teeuw W. L., Nibbering P. H., van Furth R. Pulmonary surfactant inhibits activation of human monocytes by recombinant interferon-gamma. Immunology. 1994 Jul;82(3):450–456. [PMC free article] [PubMed] [Google Scholar]
  9. Hartshorn K. L., Crouch E. C., White M. R., Eggleton P., Tauber A. I., Chang D., Sastry K. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest. 1994 Jul;94(1):311–319. doi: 10.1172/JCI117323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hartshorn K. L., Sastry K., White M. R., Anders E. M., Super M., Ezekowitz R. A., Tauber A. I. Human mannose-binding protein functions as an opsonin for influenza A viruses. J Clin Invest. 1993 Apr;91(4):1414–1420. doi: 10.1172/JCI116345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haurum J. S., Thiel S., Haagsman H. P., Laursen S. B., Larsen B., Jensenius J. C. Studies on the carbohydrate-binding characteristics of human pulmonary surfactant-associated protein A and comparison with two other collectins: mannan-binding protein and conglutinin. Biochem J. 1993 Aug 1;293(Pt 3):873–878. doi: 10.1042/bj2930873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holmskov U., Laursen S. B., Malhotra R., Wiedemann H., Timpl R., Stuart G. R., Tornøe I., Madsen P. S., Reid K. B., Jensenius J. C. Comparative study of the structural and functional properties of a bovine plasma C-type lectin, collectin-43, with other collectins. Biochem J. 1995 Feb 1;305(Pt 3):889–896. doi: 10.1042/bj3050889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holmskov U., Malhotra R., Sim R. B., Jensenius J. C. Collectins: collagenous C-type lectins of the innate immune defense system. Immunol Today. 1994 Feb;15(2):67–74. doi: 10.1016/0167-5699(94)90136-8. [DOI] [PubMed] [Google Scholar]
  14. Holmskov U., Teisner B., Willis A. C., Reid K. B., Jensenius J. C. Purification and characterization of a bovine serum lectin (CL-43) with structural homology to conglutinin and SP-D and carbohydrate specificity similar to mannan-binding protein. J Biol Chem. 1993 May 15;268(14):10120–10125. [PubMed] [Google Scholar]
  15. James P. G., Cherniak R., Jones R. G., Stortz C. A., Reiss E. Cell-wall glucans of Cryptococcus neoformans Cap 67. Carbohydr Res. 1990 Apr 2;198(1):23–38. doi: 10.1016/0008-6215(90)84273-w. [DOI] [PubMed] [Google Scholar]
  16. Knight F. R., Mackenzie D. W., Evans B. G., Porter K., Barrett N. J., White G. C. Increasing incidence of cryptococcosis in the United Kingdom. J Infect. 1993 Sep;27(2):185–191. doi: 10.1016/0163-4453(93)94863-7. [DOI] [PubMed] [Google Scholar]
  17. Kuan S. F., Rust K., Crouch E. Interactions of surfactant protein D with bacterial lipopolysaccharides. Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage. J Clin Invest. 1992 Jul;90(1):97–106. doi: 10.1172/JCI115861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuhlman M., Joiner K., Ezekowitz R. A. The human mannose-binding protein functions as an opsonin. J Exp Med. 1989 May 1;169(5):1733–1745. doi: 10.1084/jem.169.5.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lee I., Vogel F., Breen J., Friedman H. Altered responsiveness of murine lymphoid cells treated with cryptococcal capsular polysaccharide. Proc Soc Exp Biol Med. 1982 Apr;169(4):427–431. doi: 10.3181/00379727-169-41370. [DOI] [PubMed] [Google Scholar]
  20. Levitz S. M., Tabuni A., Treseler C. Effect of mannose-binding protein on binding of Cryptococcus neoformans to human phagocytes. Infect Immun. 1993 Nov;61(11):4891–4893. doi: 10.1128/iai.61.11.4891-4893.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Levitz S. M. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis. 1991 Nov-Dec;13(6):1163–1169. doi: 10.1093/clinids/13.6.1163. [DOI] [PubMed] [Google Scholar]
  22. Lu J. H., Thiel S., Wiedemann H., Timpl R., Reid K. B. Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q. J Immunol. 1990 Mar 15;144(6):2287–2294. [PubMed] [Google Scholar]
  23. Malhotra R., Haurum J., Thiel S., Jensenius J. C., Sim R. B. Pollen grains bind to lung alveolar type II cells (A549) via lung surfactant protein A (SP-A). Biosci Rep. 1993 Apr;13(2):79–90. doi: 10.1007/BF01145960. [DOI] [PubMed] [Google Scholar]
  24. Malhotra R., Haurum J., Thiel S., Sim R. B. Interaction of C1q receptor with lung surfactant protein A. Eur J Immunol. 1992 Jun;22(6):1437–1445. doi: 10.1002/eji.1830220616. [DOI] [PubMed] [Google Scholar]
  25. Malhotra R., Thiel S., Reid K. B., Sim R. B. Human leukocyte C1q receptor binds other soluble proteins with collagen domains. J Exp Med. 1990 Sep 1;172(3):955–959. doi: 10.1084/jem.172.3.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McNeely T. B., Coonrod J. D. Comparison of the opsonic activity of human surfactant protein A for Staphylococcus aureus and Streptococcus pneumoniae with rabbit and human macrophages. J Infect Dis. 1993 Jan;167(1):91–97. doi: 10.1093/infdis/167.1.91. [DOI] [PubMed] [Google Scholar]
  27. Mitchell T. G., Friedman L. In vitro phagocytosis and intracellular fate of variously encapsulated strains of Cryptococcus neoformans. Infect Immun. 1972 Apr;5(4):491–498. doi: 10.1128/iai.5.4.491-498.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miyamura K., Malhotra R., Hoppe H. J., Reid K. B., Phizackerley P. J., Macpherson P., López Bernal A. Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and localization in the fetal membranes. Biochim Biophys Acta. 1994 Jan 20;1210(3):303–307. doi: 10.1016/0005-2760(94)90233-x. [DOI] [PubMed] [Google Scholar]
  29. Reiss E., White E. H., Cherniak R., Dix J. E. Ultrastructure of acapsular mutant Cryptococcus neoformans cap 67 and monosaccharide composition of cell extracts. Mycopathologia. 1986 Jan;93(1):45–54. doi: 10.1007/BF00437014. [DOI] [PubMed] [Google Scholar]
  30. Schweinle J. E., Ezekowitz R. A., Tenner A. J., Kuhlman M., Joiner K. A. Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella. J Clin Invest. 1989 Dec;84(6):1821–1829. doi: 10.1172/JCI114367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Super M., Thiel S., Lu J., Levinsky R. J., Turner M. W. Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet. 1989 Nov 25;2(8674):1236–1239. doi: 10.1016/s0140-6736(89)91849-7. [DOI] [PubMed] [Google Scholar]
  32. Van Iwaarden J. F., Shimizu H., Van Golde P. H., Voelker D. R., Van Golde L. M. Rat surfactant protein D enhances the production of oxygen radicals by rat alveolar macrophages. Biochem J. 1992 Aug 15;286(Pt 1):5–8. doi: 10.1042/bj2860005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vartivarian S. E., Reyes G. H., Jacobson E. S., James P. G., Cherniak R., Mumaw V. R., Tingler M. J. Localization of mannoprotein in Cryptococcus neoformans. J Bacteriol. 1989 Dec;171(12):6850–6852. doi: 10.1128/jb.171.12.6850-6852.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Washburn R. G., Bryant-Varela B. J., Julian N. C., Bennett J. E. Differences in Cryptococcus neoformans capsular polysaccharide structure influence assembly of alternative complement pathway C3 convertase on fungal surfaces. Mol Immunol. 1991 Apr-May;28(4-5):465–470. doi: 10.1016/0161-5890(91)90160-l. [DOI] [PubMed] [Google Scholar]
  35. Wright J. R., Youmans D. C. Pulmonary surfactant protein A stimulates chemotaxis of alveolar macrophage. Am J Physiol. 1993 Apr;264(4 Pt 1):L338–L344. doi: 10.1152/ajplung.1993.264.4.L338. [DOI] [PubMed] [Google Scholar]
  36. Young B. J., Kozel T. R. Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect Immun. 1993 Jul;61(7):2966–2972. doi: 10.1128/iai.61.7.2966-2972.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zimmerman P. E., Voelker D. R., McCormack F. X., Paulsrud J. R., Martin W. J., 2nd 120-kD surface glycoprotein of Pneumocystis carinii is a ligand for surfactant protein A. J Clin Invest. 1992 Jan;89(1):143–149. doi: 10.1172/JCI115554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Iwaarden J. F., van Strijp J. A., Ebskamp M. J., Welmers A. C., Verhoef J., van Golde L. M. Surfactant protein A is opsonin in phagocytosis of herpes simplex virus type 1 by rat alveolar macrophages. Am J Physiol. 1991 Aug;261(2 Pt 1):L204–L209. doi: 10.1152/ajplung.1991.261.2.L204. [DOI] [PubMed] [Google Scholar]
  39. van Iwaarden J. F., van Strijp J. A., Visser H., Haagsman H. P., Verhoef J., van Golde L. M. Binding of surfactant protein A (SP-A) to herpes simplex virus type 1-infected cells is mediated by the carbohydrate moiety of SP-A. J Biol Chem. 1992 Dec 15;267(35):25039–25043. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES