Previous Article | Next Article 
Infection and Immunity, September 1999, p. 4620-4627, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Capsule of Cryptococcus neoformans Reduces
T-Lymphocyte Proliferation by Reducing Phagocytosis, Which Can Be
Restored with Anticapsular Antibody
Rachel M.
Syme,1
Tony F.
Bruno,1
Thomas R.
Kozel,2 and
Christopher H.
Mody1,3,*
Department of Microbiology and Infectious
Diseases1 and Department of Internal
Medicine,3 University of Calgary, Calgary,
Alberta, Canada T2N 4N1, and Department of Microbiology,
University of Nevada, Reno, Nevada 595572
Received 28 December 1998/Returned for modification 27 January
1999/Accepted 3 June 1999
Cell-mediated immunity is critical for the host defense to
Cryptococcus neoformans, as demonstrated by numerous
animal studies and the prevalence of the infection in AIDS patients.
Previous studies have established that the polysaccharide capsule
contributes to the virulence of C. neoformans by
suppressing T-lymphocyte proliferation, which reflects the clonal
expansion of T lymphocytes that is a hallmark of cell-mediated
immunity. The present studies were performed to identify the major
mechanism by which polysaccharide impairs lymphocyte proliferation,
since capsular polysaccharide has the potential to affect the
development of T-lymphocyte responses by stimulating production
of interleukin-10 (IL-10), inhibiting phagocytosis, and inducing
shedding of cell surface receptors. We demonstrate that polysaccharide
inhibits lymphocyte proliferation predominantly by blocking uptake
of C. neoformans, which is crucial for subsequent
lymphocyte proliferation. In addition, we show that polysaccharide did
not suppress lymphocyte proliferation via an IL-10-dependent
mechanism, nor did it affect critical surface receptor interactions on
the T cell or antigen-presenting cell. Having established that
polysaccharide impairs phagocytosis, we performed studies to determine
whether opsonization with human serum or with anticapsular antibody
could reverse this effect. Impaired uptake and lymphocyte proliferation
that were induced by polysaccharide can be enhanced through
opsonization with monoclonal antibodies or human serum, suggesting that
antipolysaccharide antibodies might enhance the host defense by
restoring uptake of the organism and subsequent presentation to T
lymphocytes. These studies support the therapeutic potential of
stimulating cell-mediated immunity to C. neoformans with
anticapsular antibody.
*
Corresponding author. Mailing address: Division of
Pulmonary Medicine, Room 273, Heritage Medical Research Building,
University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, Canada
T2N 4N1. Phone: (403) 220-5979. Fax: (403) 270-2772. E-mail:
cmody{at}ucalgary.ca.
Infection and Immunity, September 1999, p. 4620-4627, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
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]
-
Marr, K. J., Jones, G. J., Zheng, C., Huston, S. M., Timm-McCann, M., Islam, A., Berenger, B. M., Ma, L. L., Wiseman, J. C. D., Mody, C. H.
(2009). Cryptococcus neoformans Directly Stimulates Perforin Production and Rearms NK Cells for Enhanced Anticryptococcal Microbicidal Activity. Infect. Immun.
77: 2436-2446
[Abstract]
[Full Text]
-
Jain, N., Li, L., Hsueh, Y.-P., Guerrero, A., Heitman, J., Goldman, D. L., Fries, B. C.
(2009). Loss of Allergen 1 Confers a Hypervirulent Phenotype That Resembles Mucoid Switch Variants of Cryptococcus neoformans. Infect. Immun.
77: 128-140
[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]
-
Monari, C., Kozel, T. R., Paganelli, F., Pericolini, E., Perito, S., Bistoni, F., Casadevall, A., Vecchiarelli, A.
(2006). Microbial Immune Suppression Mediated by Direct Engagement of Inhibitory Fc Receptor. J. Immunol.
177: 6842-6851
[Abstract]
[Full Text]
-
Martinez, L. R., Casadevall, A.
(2005). Specific Antibody Can Prevent Fungal Biofilm Formation and This Effect Correlates with Protective Efficacy. Infect. Immun.
73: 6350-6362
[Abstract]
[Full Text]
-
Monari, C., Pericolini, E., Bistoni, G., Casadevall, A., Kozel, T. R., Vecchiarelli, A.
(2005). Cryptococcus neoformans Capsular Glucuronoxylomannan Induces Expression of Fas Ligand in Macrophages. J. Immunol.
174: 3461-3468
[Abstract]
[Full Text]
-
Syme, R. M., Spurrell, J. C. L., Amankwah, E. K., Green, F. H. Y., Mody, C. H.
(2002). Primary Dendritic Cells Phagocytose Cryptococcus neoformans via Mannose Receptors and Fc{gamma} Receptor II for Presentation to T Lymphocytes. Infect. Immun.
70: 5972-5981
[Abstract]
[Full Text]
-
Shapiro, S., Beenhouwer, D. O., Feldmesser, M., Taborda, C., Carroll, M. C., Casadevall, A., Scharff, M. D.
(2002). Immunoglobulin G Monoclonal Antibodies to Cryptococcus neoformans Protect Mice Deficient in Complement Component C3. Infect. Immun.
70: 2598-2604
[Abstract]
[Full Text]
-
Feldmesser, M., Mednick, A., Casadevall, A.
(2002). Antibody-Mediated Protection in Murine Cryptococcus neoformans Infection Is Associated with Pleotrophic Effects on Cytokine and Leukocyte Responses. Infect. Immun.
70: 1571-1580
[Abstract]
[Full Text]
-
Ma, L. L., Mody, C. H.
(2002). When There Is a Fungus Among Us, What Makes it Virulent?. Am. J. Respir. Cell Mol. Bio.
26: 273-276
[Full Text]
-
Syme, R. M., Spurrell, J. C. L., Ma, L. L., Green, F. H. Y., Mody, C. H.
(2000). Phagocytosis and Protein Processing Are Required for Presentation of Cryptococcus neoformans Mitogen to T Lymphocytes. Infect. Immun.
68: 6147-6153
[Abstract]
[Full Text]
-
Feldmesser, M., Rivera, J., Kress, Y., Kozel, T. R., Casadevall, A.
(2000). Antibody Interactions with the Capsule of Cryptococcus neoformans. Infect. Immun.
68: 3642-3650
[Abstract]
[Full Text]