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Oral carriage of Candida albicans in murine AIDS
N Deslauriers1, L Côté, S Montplaisir
1Faculty of Dental Medicine, Laval University, Quebec, Canada.
Abstract:
Oral candidiasis is a common fungal infection in patients infected with the human immunodeficiency virus (HIV). Although rare at the time of primary HIV infection, it is frequently found throughout the asymptomatic phase and is predictive of progressive immunodeficiency. However, the precise immune defect which results in outgrowth of commensal Candida albicans in HIV infection has not been identified. Mice infected with the Du5H(G6T2) mixture of mouse leukemia viruses develop a syndrome, designated murine AIDS (MAIDS), that has many of the immune abnormalities found in HIV infection. Retrovirus-infected C57BL/6 mice were examined for their ability to resist the development of oral candidiasis from the carrier state established after a self-limiting acute infection and to clear a subsequent secondary inoculum of oral C. albicans. Most of the mice orally colonized with C. albicans and then inoculated with the retrovirus mixture maintained a low-level oral carriage of C. albicans, while 30% of coinfected mice developed recurring 2- to 3-week episodes of acute Candida proliferation, separated by transient recoveries to the carrier state. The frequencies of CD4+ and CD8+ lymphocytes were, respectively, unchanged and significantly decreased (P < 0.05) in both cervical lymph nodes and spleens of coinfected mice compared to the corresponding frequencies in C. albicans-carrying, virus-free, age-matched control animals. Secretion of gamma interferon by concanavalin A (ConA)-stimulated spleen cells from Candida-carrying, retrovirus-infected mice was significantly decreased (P < 0.05) compared to that of C. albicans-carrying, retrovirus-free mice, in accordance with known abnormalities associated with MAIDS. However, production of this cytokine by ConA-stimulated or unstimulated cervical lymph node cells from coinfected mice was enhanced compared to that of virus-free animals colonized with C. albicans. Acquired resistance to reinfection with C. albicans was maintained in retrovirus-infected mice and was associated with a mucosal recruitment of CD8+ cells not observed in control mice. These results suggest that alterations in mucosal immunity which occur in MAIDS differ substantially from defects observed at other sites and that surrogate epithelial defense mechanisms may function locally to limit Candida proliferation.
Insights
Oral candidiasis in human immunodeficiency virus (HIV) infection is linked to immune defects. Murine AIDS (MAIDS) models show altered mucosal immunity, with CD8+ T-cell recruitment potentially limiting Candida proliferation despite systemic immune changes.
Area of Science:
- Immunology
- Infectious Diseases
- Virology
Background:
- Oral candidiasis is a common opportunistic infection in human immunodeficiency virus (HIV)-infected individuals, often predicting immunodeficiency progression.
- The specific immune deficiencies leading to Candida albicans overgrowth in HIV are not fully understood.
- Murine acquired immunodeficiency syndrome (MAIDS), induced by retroviruses, mimics many immune abnormalities seen in HIV infection.
Purpose of the Study:
- To investigate oral candidiasis resistance and clearance in a murine model of acquired immunodeficiency.
- To examine immune cell populations and cytokine production in retrovirus-infected mice with oral candidiasis.
- To explore the role of mucosal immunity in controlling Candida albicans in the context of MAIDS.
Main Methods:
- Mice were colonized with Candida albicans and subsequently infected with a retrovirus mixture causing MAIDS.
- Oral carriage and proliferation of C. albicans were monitored.
- Lymphocyte populations (CD4+, CD8+) and gamma interferon secretion were analyzed in spleen and cervical lymph nodes.
Main Results:
- Most retrovirus-infected mice maintained low-level oral Candida carriage, but 30% experienced recurrent Candida proliferation.
- Coinfected mice showed decreased CD8+ lymphocyte frequencies in spleen and lymph nodes, but increased gamma interferon production in cervical lymph nodes.
- Retrovirus-infected mice retained acquired resistance to reinfection, associated with mucosal CD8+ T-cell recruitment.
Conclusions:
- Mucosal immune alterations in MAIDS differ from systemic defects, suggesting localized defense mechanisms.
- CD8+ T-cell recruitment to mucosal sites may play a role in limiting Candida proliferation despite overall immune compromise.
- This model provides insights into the complex interplay between viral infection, immune status, and opportunistic fungal infections.