Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1980 Aug;29(2):633–641. doi: 10.1128/iai.29.2.633-641.1980

Host-Etiological Agent Interactions in Intranasally and Intraperitoneally Induced Cryptococcosis in Mice

Thuang S Lim 1,, Juneann W Murphy 1, Larry K Cauley 1,
PMCID: PMC551171  PMID: 7011980

Abstract

Inbred CBA/J mice were used in developing a defined in vivo model for studying host-parasite relationships in cryptococcosis. Mice were infected either intranasally or intraperitoneally with 103 viable Cryptococcus neoformans cells. At weekly intervals over a 92-day period, C. neoformans growth profiles in the lungs, spleens, livers, and brains of the infected animals were determined. In addition, humoral and delayed-type hypersensitivity responses and cryptococcal antigen levels were assayed in these mice. Intranasally infected mice developed strong delayed-type hypersensitivity reactions in response to cryptococcal culture filtrate (CneF) antigen, and there was good correlation between acquisition of delayed-type hypersensitivity and the reduction of C. neoformans cell numbers in infected tissues. In contrast, intraperitoneally infected mice displayed greater numbers of C. neoformans cells in tissues and had somewhat suppressed delayed-type hypersensitivity responses to CneF antigen. Anticryptococcal antibodies were not detected in intranasally or intraperitoneally infected mice, but cryptococcal polysaccharide antigen titers were relatively high in both groups. The transfer of sensitized spleen cells from intranasally infected mice to syngeneic naive recipient mice resulted in the transfer of delayed-type hypersensitivity responsiveness to cryptococcal antigen in the recipients. The intranasally induced infection in mice was similar to the naturally acquired infection in humans; therefore we are proposing that this murine-cryptococcosis model would be useful in gaining a greater understanding of host-etiological agent relationships in this disease.

Full text

PDF
633

Selected References

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

  1. BENNETT J. E., HASENCLEVER H. F. CRYPTOCOCCUS NEOFORMANS POLYSACCHARIDE: STUDIES OF SEROLOGIC PROPERTIES AND ROLE IN INFECTION. J Immunol. 1965 Jun;94:916–920. [PubMed] [Google Scholar]
  2. BLOOMFIELD N., GORDON M. A., ELMENDORF D. F., Jr DETECTION OF CRYPTOCOCCUS NEOFORMANS ANTIGEN IN BODY FLUIDS BY LATEX PARTICLE AGGLUTINATION. Proc Soc Exp Biol Med. 1963 Oct;114:64–67. doi: 10.3181/00379727-114-28586. [DOI] [PubMed] [Google Scholar]
  3. Bodenhoff J. Chronic cryptococcosis in the mouse. Acta Pathol Microbiol Scand. 1969;75(1):169–176. [PubMed] [Google Scholar]
  4. Boyle W. An extension of the 51Cr-release assay for the estimation of mouse cytotoxins. Transplantation. 1968 Sep;6(6):761–764. doi: 10.1097/00007890-196809000-00002. [DOI] [PubMed] [Google Scholar]
  5. Bulmer G. S., Sans M. D. Cryptococcus neoformans. 3. Inhibition of phagocytosis. J Bacteriol. 1968 Jan;95(1):5–8. doi: 10.1128/jb.95.1.5-8.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Campbell G. D. Primary pulmonary cryptococcosis. Am Rev Respir Dis. 1966 Aug;94(2):236–243. doi: 10.1164/arrd.1966.94.2.236. [DOI] [PubMed] [Google Scholar]
  7. Cauley L. K., Murphy J. W. Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect Immun. 1979 Mar;23(3):644–651. doi: 10.1128/iai.23.3.644-651.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Debré P., Kapp J. A., Benacerraf B. Genetic control of specific immune suppression. I. Experimental conditions for the stimulation of suppressor cells by the copolymer L-glutamic acid50-L-tyrosine50 (GT) in nonresponder BALB/c mice. J Exp Med. 1975 Dec 1;142(6):1436–1446. doi: 10.1084/jem.142.6.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Diamond R. D. Effects of stimulation and suppression of cell-mediated immunity on experimental cryptococcosis. Infect Immun. 1977 Jul;17(1):187–194. doi: 10.1128/iai.17.1.187-194.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duperval R., Hermans P. E., Brewer N. S., Roberts G. D. Cryptococcosis, with emphasis on the significance of isolation of Cryptococcus neoformans from the respiratory tract. Chest. 1977 Jul;72(1):13–19. doi: 10.1378/chest.72.1.13. [DOI] [PubMed] [Google Scholar]
  11. Dykstra M. A., Friedman L. Pathogenesis, lethality, and immunizing effect of experimental cutaneous cryptococcosis. Infect Immun. 1978 May;20(2):446–455. doi: 10.1128/iai.20.2.446-455.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. GADEBUSCH H. H., WARD P. A., FRENKEL E. P. NATURAL HOST RESISTANCE TO INFECTION WITH CRYPTOCOCCUS NEOFORMANS. III. THE EFFECT OF CRYPTOCOCCAL POLYSACCHARIDE UPON THE PHYSIOLOGY OF THE RETICULOENDOTHELIAL SYSTEM OF LABORATORY ANIMALS. J Infect Dis. 1964 Feb;114:95–106. doi: 10.1093/infdis/114.1.95. [DOI] [PubMed] [Google Scholar]
  14. Gordonson J., Birnbaum W., Jacobson G., Sargent E. N. Pulmonary cryptococcosis. Radiology. 1974 Sep;112(3):557–561. doi: 10.1148/112.3.557. [DOI] [PubMed] [Google Scholar]
  15. Graybill J. R., Alford R. H. Cell-mediated immunity in Cryptococcosis. Cell Immunol. 1974 Oct;14(1):12–21. doi: 10.1016/0008-8749(74)90164-6. [DOI] [PubMed] [Google Scholar]
  16. Graybill J. R., Taylor R. L. Host defense in cryptococcosis. I. An in vivo model for evaluating immune response. Int Arch Allergy Appl Immunol. 1978;57(2):101–113. [PubMed] [Google Scholar]
  17. Greene M. I., Pierres A., Dorf M. E., Benacerraf B. The I-J subregion codes for determinats on suppressor factor(s) which limit the contact sensitivity response to picryl chloride. J Exp Med. 1977 Jul 1;146(1):293–296. doi: 10.1084/jem.146.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hatcher C. R., Jr, Sehdeva J., Waters W. C., 3rd, Schulze V., Symbas P., Logan W. D., Jr, Abbott O. A. Primary pulmonary cryptococcosis. J Thorac Cardiovasc Surg. 1971 Jan;61(1):39–49. [PubMed] [Google Scholar]
  19. Hay R. J., Reiss E. Delayed-type hypersensitivity responses in infected mice elicited by cytoplasmic fractions of Cryptococcus neoformans. Infect Immun. 1978 Oct;22(1):72–79. doi: 10.1128/iai.22.1.72-79.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. KATZ R. I., BIRNBAUM H., ECKMANN B. H. Resection of pulmonary crytococcosis associated with meningitis. Am Rev Respir Dis. 1961 Nov;84:725–729. doi: 10.1164/arrd.1961.84.5P1.725. [DOI] [PubMed] [Google Scholar]
  21. Karaoui R. M., Hall N. K., Larsh H. W. Role of macrophages in immunity and pathogenesis of experimental cryptococcosis induced by the airborne route.--Part I: Pathogenesis and acquired immunity of Cryptococcus neoformans. Mykosen. 1977 Oct;20(10):380–388. [PubMed] [Google Scholar]
  22. Kozel T. R., Mastroianni R. P. Inhibition of phagocytosis by cryptococcal polysaccharide: dissociation of the attachment and ingestion phases of phagocytosis. Infect Immun. 1976 Jul;14(1):62–67. doi: 10.1128/iai.14.1.62-67.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lefford M. J. Induction and expression of immunity after BCG immunization. Infect Immun. 1977 Dec;18(3):646–653. doi: 10.1128/iai.18.3.646-653.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lewis J. L., Rabinovich S. The wide spectrum of cryptococcal infections. Am J Med. 1972 Sep;53(3):315–322. doi: 10.1016/0002-9343(72)90174-x. [DOI] [PubMed] [Google Scholar]
  25. Littman M. L., Walter J. E. Cryptococcosis: current status. Am J Med. 1968 Dec;45(6):922–932. doi: 10.1016/0002-9343(68)90190-3. [DOI] [PubMed] [Google Scholar]
  26. Miller S. D., Wetzig R. P., Claman H. N. The induction of cell-mediated immunity and tolerance with protein antigens coupled to syngeneic lymphoid cells. J Exp Med. 1979 Mar 1;149(3):758–773. doi: 10.1084/jem.149.3.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Moorhead J. W. Soluble factors in tolerance and contact sensitivity to 2,4-dinitrofluorobenzene in mice. I. Suppression of contact sensitivity by soluble suppressor factor released in vitro by lymph node cell populations containing specific suppressor cells. J Immunol. 1977 Jul;119(1):315–321. [PubMed] [Google Scholar]
  28. 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]
  29. NEILL J. M., SUGG J. Y., McCAULEY D. W. Serologically reactive material in spinal fluid, blood, and urine from a human case of cryptococcosis (torulosis). Proc Soc Exp Biol Med. 1951 Aug;77(4):775–778. doi: 10.3181/00379727-77-18924. [DOI] [PubMed] [Google Scholar]
  30. Neilson J. B., Fromtling R. A., Bulmer G. S. Cryptococcus neoformans: size range of infectious particles from aerosolized soil. Infect Immun. 1977 Sep;17(3):634–638. doi: 10.1128/iai.17.3.634-638.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. PERCEVAL A. K. EXPERIMENTAL CRYPTOCOCCOSIS: HYPERSENSITIVITY AND IMMUNITY. J Pathol Bacteriol. 1965 Apr;89:645–655. doi: 10.1002/path.1700890225. [DOI] [PubMed] [Google Scholar]
  32. RITTER R. C., LARSH H. W. THE INFECTION OF WHITE MICE FOLLOWING AN INTRANASAL INSTILLATION OF CRYPTOCOCCUS NEOFORMANS. Am J Hyg. 1963 Sep;78:241–246. doi: 10.1093/oxfordjournals.aje.a120342. [DOI] [PubMed] [Google Scholar]
  33. Riley D. J., Edelman N. H. Hemoptysis in pulmonary cryptococcosis. J Med Soc N J. 1978 Jul;75(7):553–555. [PubMed] [Google Scholar]
  34. SMITH C. D., RITTER R., LARSH H. W., FURCOLOW M. L. INFECTION OF WHITE SWISS MICE WITH AIRBORNE CRYPTOCOCCUS NEOFORMANS. J Bacteriol. 1964 Jun;87:1364–1368. doi: 10.1128/jb.87.6.1364-1368.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schimpff S. C., Bennett J. E. Abnormalities in cell-mediated immunity in patients with Cryptococcus neoformans infection. J Allergy Clin Immunol. 1975 Jun;55(6):430–441. doi: 10.1016/0091-6749(75)90082-2. [DOI] [PubMed] [Google Scholar]
  36. Staib F., Grave B., Altmann L., Mishra S. K., Abel T., Blisse A. Epidemiology of Cryptococcus neoformans. Mycopathologia. 1978 Dec 18;65(1-3):73–76. doi: 10.1007/BF00447178. [DOI] [PubMed] [Google Scholar]
  37. Taniguchi M., Tada T., Tokuhisa T. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. III. Dual gene control of the T-cell-mediated suppression of the antibody response. J Exp Med. 1976 Jul 1;144(1):20–31. doi: 10.1084/jem.144.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Walter J. E., Jones R. D. Serodiagnosis of clinical cryptococcosis. Am Rev Respir Dis. 1968 Feb;97(2):275–282. doi: 10.1164/arrd.1968.97.2.275. [DOI] [PubMed] [Google Scholar]

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

RESOURCES