This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Santangelo, R.
Right arrow Articles by Wright, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santangelo, R.
Right arrow Articles by Wright, L.

 Previous Article  |  Next Article 

Infection and Immunity, April 2004, p. 2229-2239, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2229-2239.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role of Extracellular Phospholipases and Mononuclear Phagocytes in Dissemination of Cryptococcosis in a Murine Model

Rosemary Santangelo,1,2 Hans Zoellner,3 Tania Sorrell,1,2 Christabel Wilson,1,2 Christine Donald,3 Julianne Djordjevic,1,2 Yi Shounan,4 and Lesley Wright1,2*

Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead,1 Department of Infectious Diseases,2 Department of Renal Medicine, Westmead Hospital,4 Cellular and Molecular Pathology Research Unit, The Department of Oral Medicine and Oral Pathology, University of Sydney at Westmead Hospital Dental Clinical School, Westmead NSW 2145, Australia3

Received 20 August 2003/ Returned for modification 24 September 2003/ Accepted 9 January 2004

Secreted phospholipase B (PLB) activity promotes the survival and replication of Cryptococcus neoformans in macrophages in vitro. We therefore investigated the role of mononuclear phagocytes and cryptococcal PLB in the dissemination of infection in a mouse model, using C. neoformans var. grubii wild-type strain H99, a PLB1 deletion mutant ({Delta}plb1), and a reconstituted strain ({Delta}plb1rec). PLB facilitated the entry of endotracheally administered cryptococci into lung IM. PLB was also required for lymphatic spread from the lung to regional lymph nodes and for entry into the blood. Langhans-type giant cells containing budding cryptococci were seen free in the lymphatic sinuses of hilar nodes of H99- and {Delta}plb1rec-infected mice, suggesting that they may have a role in the dissemination of cryptococcal infection. The transfer of infected lung macrophages to recipient mice by tail vein injections demonstrated that these cells can facilitate hematogenous dissemination of cryptococci to the brain, independent of cryptococcal PLB secretion. PLB activities of cryptococci isolated from lung macrophages or infected brains were not persistently increased. We conclude that mononuclear phagocytes are a vehicle for cryptococcal dissemination and that PLB activity is necessary for the initiation of interstitial pulmonary infections and for dissemination from the lung via the lymphatics and blood. PLB is not, however, essential for the establishment of neurological infections when cryptococci are presented within, or after passage through, mononuclear phagocytes.

* Corresponding author. Mailing address: Centre for Infectious Diseases and Microbiology, Level 3, ICPMR Building, Westmead Hospital, Westmead NSW 2145, Australia. Phone: 612-98457367. Fax: 612-98915317. E-mail: lesleyw{at}icpmr.wsahs.nsw.gov.au.

Editor: T. R. Kozel

Infection and Immunity, April 2004, p. 2229-2239, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2229-2239.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Voelz, K., Lammas, D. A., May, R. C. (2009). Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism by Cryptococcus neoformans. Infect. Immun. 77: 3450-3457 [Abstract] [Full Text]  
  • Geunes-Boyer, S., Oliver, T. N., Janbon, G., Lodge, J. K., Heitman, J., Perfect, J. R., Wright, J. R. (2009). Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival. Infect. Immun. 77: 2783-2794 [Abstract] [Full Text]  
  • Means, T. K., Mylonakis, E., Tampakakis, E., Colvin, R. A., Seung, E., Puckett, L., Tai, M. F., Stewart, C. R., Pukkila-Worley, R., Hickman, S. E., Moore, K. J., Calderwood, S. B., Hacohen, N., Luster, A. D., El Khoury, J. (2009). Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. JEM 206: 637-653 [Abstract] [Full Text]  
  • Charlier, C., Nielsen, K., Daou, S., Brigitte, M., Chretien, F., Dromer, F. (2009). Evidence of a Role for Monocytes in Dissemination and Brain Invasion by Cryptococcus neoformans. Infect. Immun. 77: 120-127 [Abstract] [Full Text]  
  • Siafakas, A. R., Sorrell, T. C., Wright, L. C., Wilson, C., Larsen, M., Boadle, R., Williamson, P. R., Djordjevic, J. T. (2007). Cell Wall-linked Cryptococcal Phospholipase B1 Is a Source of Secreted Enzyme and a Determinant of Cell Wall Integrity. J. Biol. Chem. 282: 37508-37514 [Abstract] [Full Text]  
  • Zaragoza, O., Alvarez, M., Telzak, A., Rivera, J., Casadevall, A. (2007). The Relative Susceptibility of Mouse Strains to Pulmonary Cryptococcus neoformans Infection Is Associated with Pleiotropic Differences in the Immune Response. Infect. Immun. 75: 2729-2739 [Abstract] [Full Text]  
  • Tong, Z., Widmer, F., Sorrell, T. C., Guse, Z., Jolliffe, K. A., Halliday, C., Lee, O. C., Kong, F., Wright, L. C., Chen, S. C. A. (2007). In Vitro Activities of Miltefosine and Two Novel Antifungal Biscationic Salts against a Panel of 77 Dermatophytes. Antimicrob. Agents Chemother. 51: 2219-2222 [Abstract] [Full Text]  
  • Beenhouwer, D. O., Yoo, E. M., Lai, C.-W., Rocha, M. A., Morrison, S. L. (2007). Human Immunoglobulin G2 (IgG2) and IgG4, but Not IgG1 or IgG3, Protect Mice against Cryptococcus neoformans Infection. Infect. Immun. 75: 1424-1435 [Abstract] [Full Text]  
  • Erb-Downward, J. R., Huffnagle, G. B. (2007). Cryptococcus neoformans Produces Authentic Prostaglandin E2 without a Cyclooxygenase. Eukaryot Cell 6: 346-350 [Abstract] [Full Text]  
  • Wright, L. C., Santangelo, R. M., Ganendren, R., Payne, J., Djordjevic, J. T., Sorrell, T. C. (2007). Cryptococcal Lipid Metabolism: Phospholipase B1 Is Implicated in Transcellular Metabolism of Macrophage-Derived Lipids. Eukaryot Cell 6: 37-47 [Abstract] [Full Text]  
  • Widmer, F., Wright, L. C., Obando, D., Handke, R., Ganendren, R., Ellis, D. H., Sorrell, T. C. (2006). Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis. Antimicrob. Agents Chemother. 50: 414-421 [Abstract] [Full Text]  
  • Sanguinetti, M., Posteraro, B., La Sorda, M., Torelli, R., Fiori, B., Santangelo, R., Delogu, G., Fadda, G. (2006). Role of AFR1, an ABC Transporter-Encoding Gene, in the In Vivo Response to Fluconazole and Virulence of Cryptococcus neoformans. Infect. Immun. 74: 1352-1359 [Abstract] [Full Text]  
  • da Silva, E. G., Baroni, F. d. A., Viani, F. C., Ruiz, L. d. S., Gandra, R. F., Auler, M. E., Dias, A. L. T., Gambale, W., Paula, C. R. (2006). Virulence profile of strains of Cryptococcus neoformans var. grubii evaluated by experimental infection in BALB/c mice and correlation with exoenzyme activity. J Med Microbiol 55: 139-142 [Abstract] [Full Text]  
  • Nielsen, K., Cox, G. M., Litvintseva, A. P., Mylonakis, E., Malliaris, S. D., Benjamin, D. K. Jr., Giles, S. S., Mitchell, T. G., Casadevall, A., Perfect, J. R., Heitman, J. (2005). Cryptococcus neoformans {alpha} Strains Preferentially Disseminate to the Central Nervous System during Coinfection. Infect. Immun. 73: 4922-4933 [Abstract] [Full Text]  
  • Charlier, C., Chretien, F., Baudrimont, M., Mordelet, E., Lortholary, O., Dromer, F. (2005). Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier. Am. J. Pathol. 166: 421-432 [Abstract] [Full Text]  
  • Chang, Y. C., Stins, M. F., McCaffery, M. J., Miller, G. F., Pare, D. R., Dam, T., Paul-Satyasee, M., Kim, K. S., Kwon-Chung, K. J. (2004). Cryptococcal Yeast Cells Invade the Central Nervous System via Transcellular Penetration of the Blood-Brain Barrier. Infect. Immun. 72: 4985-4995 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»