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 Zaragoza, O.
Right arrow Articles by Casadevall, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zaragoza, O.
Right arrow Articles by Casadevall, A.

 Previous Article  |  Next Article 

Infection and Immunity, June 2007, p. 2729-2739, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.00094-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Relative Susceptibility of Mouse Strains to Pulmonary Cryptococcus neoformans Infection Is Associated with Pleiotropic Differences in the Immune Response{triangledown}

Oscar Zaragoza,1,{dagger} Mauricio Alvarez,1 Andrew Telzak,1 Johanna Rivera,1 and Arturo Casadevall1,2*

Departments of Microbiology and Immunology,1 Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 104612

Received 17 January 2007/ Returned for modification 14 February 2007/ Accepted 6 March 2007

CBA/J mice were highly susceptible to intratracheal (i.t.) Cryptococcus neoformans infection relative to BALB/c mice, while both strains were equally susceptible to intravenous (i.v.) infection. Increased susceptibility in i.t. infection was associated with higher brain CFU, lower serum immunoglobulin M (IgM) and IgG responses to glucuronoxylomannan (GXM), lack of IgE regulation during infection, and alveolar macrophage permissiveness to intracellular replication in vitro. In contrast, for BALB/c mice, relative resistance was associated with increased interleukin-12 (IL-12) and decreased IL-10 pulmonary levels. In CBA/J mice, relative susceptibility was associated with a decreased proportion of CD4+ and CD8+ T cells and an increase in macrophage percentage in pulmonary infiltrates. In contrast, no significant differences in these cytokines or cell recruitment were observed in the i.v. model, consistent with no differences in the survival rate. Passive antibody (Ab) protection experiments revealed a prozone effect in the BALB/c mice with i.v. infection, such that Ab efficacy decreased at higher doses. In the i.t. model using CBA/J mice, low Ab doses were disease enhancing and protection was observed only at high doses. Our results show (i) that differences in mouse strain susceptibility are a function of the infection model, (ii) that susceptibility to pulmonary infection was associated with macrophage permissiveness for intracellular replication, and (iii) that the efficacy of passive Ab in pulmonary infection is a function of dose and mouse strain. The results highlight significant differences in the pathogenesis of cryptococcal infection among inbred mice and associate their relative susceptibility with differences in numerous components of the innate and adaptive immune responses.

* Corresponding author. Mailing address: Departments of Microbiology and Immunology and Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-3665. Fax: (718) 430-8701. E-mail: casadeva{at}aecom.yu.edu

{triangledown} Published ahead of print on 19 March 2007.

Editor: J. N. Weiser

{dagger} Present address: Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera de Majadahonda-Pozuelo, Km2, Majadahonda 28220, Madrid, Spain.

Infection and Immunity, June 2007, p. 2729-2739, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.00094-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cheng, P.-Y., Sham, A., Kronstad, J. W. (2009). Cryptococcus gattii Isolates from the British Columbia Cryptococcosis Outbreak Induce Less Protective Inflammation in a Murine Model of Infection than Cryptococcus neoformans. Infect. Immun. 77: 4284-4294 [Abstract] [Full Text]  
  • Litvintseva, A. P., Mitchell, T. G. (2009). Most Environmental Isolates of Cryptococcus neoformans var. grubii (Serotype A) Are Not Lethal for Mice. Infect. Immun. 77: 3188-3195 [Abstract] [Full Text]  
  • Guillot, L., Carroll, S. F., Homer, R., Qureshi, S. T. (2008). Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection. Infect. Immun. 76: 4745-4756 [Abstract] [Full Text]  
  • Guerrero, A., Fries, B. C. (2008). Phenotypic Switching in Cryptococcus neoformans Contributes to Virulence by Changing the Immunological Host Response. Infect. Immun. 76: 4322-4331 [Abstract] [Full Text]  
  • Chen, G.-h., McNamara, D. A., Hernandez, Y., Huffnagle, G. B., Toews, G. B., Olszewski, M. A. (2008). Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility to Cryptococcus neoformans in a Mouse Model. Infect. Immun. 76: 2379-2391 [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»