Enhanced allergic inflammation and airway responsiveness in rats with chronic Cryptococcus neoformans infection:: Potential role for fungal pulmonary infection in the pathogenesis of asthma

Although Cryptococcus neoformans is recognized for its ability to cause meningoencephalitis and pneumonia among immunocompromised persons, subclinical pulmonary infection is also common among immunocompetent persons. The significance of this infection is unknown. Using a rat model, we explored the potential for pulmonary cryptococcosis to modify allergic responses and airway reactivity. Our findings indicate that localized pulmonary cryptococcal infection ( but not disseminated infection) can exacerbate allergic responses to respiratory challenge with ovalbumin, as measured by total immunoglobulin E levels, ovalbumin-specific immunoglobulin E titers, and eosinophil content of bronchoalveolar lavage fluid. Infection-associated enhancement of allergic responses was not dependent on cryptococcal encapsulation and was partially ameliorated by the administration of fluconazole. Increases in both the number of goblet cells and airway responsiveness, which are also features of reactive airway disease, were also present with pulmonary infection. An examination of lung cytokine levels in the context of active pulmonary infection revealed increased expression of interleukin (IL)-10, tumor necrosis factor-alpha, and IL-13, but not IL-12 or interferon-gamma. In contrast, systemic infection was associated with higher levels of interferon-gamma but lower levels of IL-13. Our studies highlight the potential for localized pulmonary C. neoformans infection to potentiate allergic responses and airway reactivity and suggest a potential role for subclinical pulmonary cryptococcosis in the pathogenesis of asthma.