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Infection and Immunity, October 2000, p. 5771-5777, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Cellular and Cytokine Correlates of Mucosal Protection in Murine Model of Oral Candidiasis

Shokrollah Elahi,1 Gerald Pang,1 Robert Clancy,1,* and Robert B. Ashman2

Discipline of Immunology and Microbiology, University of Newcastle, Newcastle, New South Wales, 2300,1 and School of Dentistry, University of Queensland, Brisbane, Queensland 4072,2 Australia

Received 11 May 2000/Accepted 7 June 2000

Host protection against Candida albicans infection in a model of oral candidiasis involving infection-prone [DBA/2 (H-2d)] and less infection-prone [BALB/c (H-2d)] mouse strains was analyzed in terms of antibody and cellular responses, and in terms of cytokine patterns from regional lymph node cells. There was a selective expansion of gamma /delta + T-cell receptor cells, which correlated with the patterns of colonization in both mouse strains, with higher numbers of gamma /delta T cells detected in BALB/c mice. Antigen-induced T-cell proliferation was significantly higher in BALB/c mice than in DBA/2 mice. Higher levels of serum immunoglobulin G (IgG) and salivary IgA antibodies were detected in BALB/c mice than in DBA/2 mice, but only after the infection was cleared. The cervical lymph node cells from infected mice were assessed for interleukin-4 (IL-4), IL-12, and gamma interferon (IFN-gamma ) mRNA gene expression by reverse transcription-PCR and protein production in the culture supernatants following restimulation in vitro. In BALB/c mice, an early increase in levels of IL-4, IFN-gamma , and IL-12 correlated with rapid elimination of C. albicans. In DBA/2 mice, where resolution of infection was delayed, IL-4 message expression was delayed and the IL-4 secretion level was lower. Neutralization of IL-4 by multiple injections of an anti-IL-4 monoclonal antibody in BALB/c mice resulted in increased carriage rate and delayed clearance of the yeasts. Collectively, the data suggest that the T-cell response to C. albicans in the regional lymph nodes which correlates best with rapid oral clearance of C. albicans is a balanced Th0 cytokine response involving early secretion of both IFN-gamma and IL-4.

* Corresponding author. Mailing address: Discipline of Immunology and Microbiology, Faculty of Medicine and Health Sciences, David Maddison Clinical Science Building, Royal Newcastle Hospital, Newcastle, NSW 2300, Australia. Phone: 61 2 49 236 135. Fax: 61 2 49 236 998. E-mail: rclancy{at}mail.newcastle.edu.au.

Infection and Immunity, October 2000, p. 5771-5777, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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