TY - JOUR
T1 - Enhanced allergic inflammation and airway responsiveness in rats with chronic Cryptococcus neoformans infection
T2 - Potential role for fungal pulmonary infection in the pathogenesis of asthma
AU - Goldman, David L.
AU - Davis, Jennifer
AU - Bommarito, Frank
AU - Shao, Xiuping
AU - Casadevall, Arturo
N1 - Funding Information:
Received 2 December 2004; accepted 5 November 2005; electronically published 9 March 2006. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grants AI-33774, AI-3342, and HL-59842 to A.C. and grant HL-64547 to D.L.G.). Reprints or correspondence: Dr. David L. Goldman, Albert Einstein College of Medicine, Dept. of Pediatrics, 1300 Morris Park Ave., Bronx, NY 10461 (dgoldma@ aecom.yu.edu).
PY - 2006/4/15
Y1 - 2006/4/15
N2 - 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-α, and IL-13, but not IL-12 or interferon-γ. In contrast, systemic infection was associated with higher levels of interferon-γ 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.
AB - 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-α, and IL-13, but not IL-12 or interferon-γ. In contrast, systemic infection was associated with higher levels of interferon-γ 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.
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U2 - 10.1086/501363
DO - 10.1086/501363
M3 - Article
C2 - 16544260
AN - SCOPUS:33645761624
SN - 0022-1899
VL - 193
SP - 1178
EP - 1186
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 8
ER -