Abstract
Cryptococcus neoformans var. gattii (serotype B and C) isolates have a relative predilection for immunocompetent hosts, and C. neoformans var. neoformans (serotype A and D) isolates have a relative predilection for immunocompromised hosts, suggesting that normal host resistance to the former may be relatively inefficient compared with that to the latter variety. In order to assess the possibility that normal cellular host defense is inadequate in protecting against C. neoformans var. gattii, we compared the two varieties of C. neoformans cells and their culture filtrate antigens (CneF) with respect to effects on neutrophil (polymorphonuclear leukocyte [PMN]) locomotion. In a 48-well modified Boyden chamber, the cells and CneF of C. neoformans var. neoformans (serotype A and D) isolates stimulated chemotaxis and chemokinesis of human PMN and activated a complement component(s) in pooled human serum to become a chemoattractant(s) for human PMN. In contrast, the cells and CneF of C. neoformans var. gattii (serotype B and C) isolates did not stimulate chemotaxis or chemokinesis in human PMN but rather inhibited chemokinesis and chemotactic responses of PMN to pooled human serum and formylmethionyl leucyl phenylalanine. Neither of the CneF from the C. neoformans var. gattii isolates was cytotoxic to PMN. Furthermore, with the mouse model, we found that CneF from C. neoformans var. neoformans caused migration of PMN into gelatin sponges implanted in naive and immunized mice, whereas CneF from C. neoformans var. gattii inhibited PMN migration into sponges. Our results, combined with findings of others showing reduced PMN infiltration in lungs of mice infected with C. neoformans var. gattii compared with PMN infiltration in lungs of mice infected with C. neoformans var. neoformans, indicate that the relative inadequacy of normal host resistance mechanisms to prevent infection with C. neoformans var. gattii results, in part, from inhibition of PMN migration to the site of the organism.
Full Text
The Full Text of this article is available as a PDF (354.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bennett J. E., Kwon-Chung K. J., Theodore T. S. Biochemical differences between serotypes of Cryptococcus neoformans. Sabouraudia. 1978 Sep;16(3):167–174. [PubMed] [Google Scholar]
- 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]
- Buchanan K. L., Murphy J. W. Characterization of cellular infiltrates and cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response. Infect Immun. 1993 Jul;61(7):2854–2865. doi: 10.1128/iai.61.7.2854-2865.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cherniak R., Sundstrom J. B. Polysaccharide antigens of the capsule of Cryptococcus neoformans. Infect Immun. 1994 May;62(5):1507–1512. doi: 10.1128/iai.62.5.1507-1512.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diamond R. D., Bennett J. E. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. doi: 10.7326/0003-4819-80-2-176. [DOI] [PubMed] [Google Scholar]
- Dong Z. M., Murphy J. W. Mobility of human neutrophils in response to Cryptococcus neoformans cells, culture filtrate antigen, and individual components of the antigen. Infect Immun. 1993 Dec;61(12):5067–5077. doi: 10.1128/iai.61.12.5067-5077.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellis D. H., Pfeiffer T. J. Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol. 1990 Jul;28(7):1642–1644. doi: 10.1128/jcm.28.7.1642-1644.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eng R. H., Bishburg E., Smith S. M., Kapila R. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med. 1986 Jul;81(1):19–23. doi: 10.1016/0002-9343(86)90176-2. [DOI] [PubMed] [Google Scholar]
- Harvath L., Falk W., Leonard E. J. Rapid quantitation of neutrophil chemotaxis: use of a polyvinylpyrrolidone-free polycarbonate membrane in a multiwell assembly. J Immunol Methods. 1980;37(1):39–45. doi: 10.1016/0022-1759(80)90179-9. [DOI] [PubMed] [Google Scholar]
- Hidore M. R., Murphy J. W. Natural cellular resistance of beige mice against Cryptococcus neoformans. J Immunol. 1986 Dec 1;137(11):3624–3631. [PubMed] [Google Scholar]
- Kwon-Chung K. J., Bennett J. E. Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol. 1984 Jul;120(1):123–130. doi: 10.1093/oxfordjournals.aje.a113861. [DOI] [PubMed] [Google Scholar]
- Kwon-Chung K. J., Wickes B. L., Booth J. L., Vishniac H. S., Bennett J. E. Urease inhibition by EDTA in the two varieties of Cryptococcus neoformans. Infect Immun. 1987 Aug;55(8):1751–1754. doi: 10.1128/iai.55.8.1751-1754.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laxalt K. A., Kozel T. R. Chemotaxigenesis and activation of the alternative complement pathway by encapsulated and non-encapsulated Cryptococcus neoformans. Infect Immun. 1979 Nov;26(2):435–440. doi: 10.1128/iai.26.2.435-440.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lovchik J. A., Lipscomb M. F. Role for C5 and neutrophils in the pulmonary intravascular clearance of circulating Cryptococcus neoformans. Am J Respir Cell Mol Biol. 1993 Dec;9(6):617–627. doi: 10.1165/ajrcmb/9.6.617. [DOI] [PubMed] [Google Scholar]
- Mello S. B., Farsky S. H., Sannomiya P., Garcia-Leme J. Inhibition of neutrophil chemotaxis and chemokinesis associated with a plasma protein in aging rats: selective depression of cell responses mediated by complement-derived chemoattractants. J Leukoc Biol. 1992 Jan;51(1):46–52. doi: 10.1002/jlb.51.1.46. [DOI] [PubMed] [Google Scholar]
- Miller M. F., Mitchell T. G. Killing of Cryptococcus neoformans strains by human neutrophils and monocytes. Infect Immun. 1991 Jan;59(1):24–28. doi: 10.1128/iai.59.1.24-28.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy J. W., Cozad G. C. Immunological unresponsiveness induced by cryptococcal capsular polysaccharide assayed by the hemolytic plaque technique. Infect Immun. 1972 Jun;5(6):896–901. doi: 10.1128/iai.5.6.896-901.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy J. W. Mechanisms of natural resistance to human pathogenic fungi. Annu Rev Microbiol. 1991;45:509–538. doi: 10.1146/annurev.mi.45.100191.002453. [DOI] [PubMed] [Google Scholar]
- Murphy J. W., Moorhead J. W. Regulation of cell-mediated immunity in cryptococcosis. I. Induction of specific afferent T suppressor cells by cryptococcal antigen. J Immunol. 1982 Jan;128(1):276–283. [PubMed] [Google Scholar]
- Murphy J. W., Mosley R. L., Cherniak R., Reyes G. H., Kozel T. R., Reiss E. Serological, electrophoretic, and biological properties of Cryptococcus neoformans antigens. Infect Immun. 1988 Feb;56(2):424–431. doi: 10.1128/iai.56.2.424-431.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rhodes J. C. Contribution of complement component C5 to the pathogenesis of experimental murine cryptococcosis. Sabouraudia. 1985 Jun;23(3):225–234. doi: 10.1080/00362178585380331. [DOI] [PubMed] [Google Scholar]
- Rot A. Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. Immunol Today. 1992 Aug;13(8):291–294. doi: 10.1016/0167-5699(92)90039-A. [DOI] [PubMed] [Google Scholar]
- Rozenbaum R., Gonçalves A. J., Wanke B., Caiuby M. J., Clemente H., Lazera M. dos S., Monteiro P. C., Londero A. T. Cryptococcus neoformans varieties as agents of cryptococcosis in Brazil. Mycopathologia. 1992 Sep;119(3):133–136. doi: 10.1007/BF00448809. [DOI] [PubMed] [Google Scholar]
- Sherry B., Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses. J Cell Biol. 1988 Oct;107(4):1269–1277. doi: 10.1083/jcb.107.4.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugar A. M. Overview: cryptococcosis in the patient with AIDS. Mycopathologia. 1991 Jun;114(3):153–157. doi: 10.1007/BF00437205. [DOI] [PubMed] [Google Scholar]
- Thurmond L. M., Mitchell T. G. Blastomyces dermatitidis chemotactic factor: kinetics of production and biological characterization evaluated by a modified neutrophil chemotaxis assay. Infect Immun. 1984 Oct;46(1):87–93. doi: 10.1128/iai.46.1.87-93.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Wickes B. L., Moore T. D., Kwon-Chung K. J. Comparison of the electrophoretic karyotypes and chromosomal location of ten genes in the two varieties of Cryptococcus neoformans. Microbiology. 1994 Mar;140(Pt 3):543–550. doi: 10.1099/00221287-140-3-543. [DOI] [PubMed] [Google Scholar]
- Xu H. B., Mei W. D., Dong Z. M., Liao B. L. Study of the oxidative metabolic function and chemotaxis of neutrophils from patients with cancer influenced by selenium yeast. Biol Trace Elem Res. 1990 Jun;25(3):201–209. doi: 10.1007/BF02990415. [DOI] [PubMed] [Google Scholar]