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Infection and Immunity, December 2009, p. 5389-5399, Vol. 77, No. 12
0019-9567/09/$08.00+0 doi:10.1128/IAI.00809-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Th2 but Not Th1 Immune Bias Results in Altered Lung Functions in a Murine Model of Pulmonary Cryptococcus neoformans Infection
Aditya V. Jain,1,
Yanmei Zhang,2,
W. Bradley Fields,1,2
David A. McNamara,1
Mun Y. Choe,1
Gwo-hsiao Chen,1,2
John Erb-Downward,2
John J. Osterholzer,1,2
Galen B. Toews,1,2
Gary B. Huffnagle,2,3,4 and
Michal A. Olszewski1,2*
Department of Veteran's Affairs Ann Arbor Healthcare System, 2215 Fuller Rd., Ann Arbor, Michigan 48105,1 Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine,2 Department of Microbiology and Immunology,3 Graduate Program in Immunology, University of Michigan Health System, 1150 W. Medical Center Drive, Ann Arbor, Michigan 481094
Received 18 July 2009/ Returned for modification 12 August 2009/ Accepted 28 August 2009
Changes in airway dynamics have been reported in the rat model of pulmonary cryptococcosis. However, it is not known if Cryptococcus neoformans-induced changes in lung functions are related to the immunophenotype that develops in response to cryptococcal infection in the lungs. In this study we performed a parallel analysis of the immunophenotype and airway resistance (standard resistance of the airways [SRAW]) in BALB/c mice infected with highly virulent C. neoformans strain H99 and moderately virulent strain 52D. H99 infection evoked a Th2 response and was associated with increased SRAW, while the SRAW for 52D infection, which resulted in a predominantly Th1-skewed response, did not differ from the SRAW for uninfected mice. We found that an altered SRAW in mice did not positively or negatively correlate with the pulmonary fungal burden, the magnitude of inflammatory response, the numbers of T cells, eosinophils or eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by lung leukocytes. However, the level of a systemic Th2 marker, serum immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the changes in lung functions were proportional to the level of Th2 skewing in this model. These data also imply that IgE may contribute to the altered SRAW observed in H99-infected mice. Lung histological analysis revealed severe allergic bronchopulmonary mycosis pathology in H99-infected mice and evidence of protective responses in 52D-infected mice with well-marginalized lesions. Taken together, the data show that C. neoformans can significantly affect airflow physiology, particularly in the context of a Th2 immune response with possible involvement of IgE as an important factor.
* Corresponding author. Mailing address: Ann Arbor Veterans Administration Health System (11R), 2215 Fuller Rd., Ann Arbor, MI 48105. Phone: (734) 845-5238. Fax: (734) 845-3241. E-mail: olszewsm{at}umich.edu
Published ahead of print on 14 September 2009.
A.V.J. and Y.Z. contributed equally to this work.
Infection and Immunity, December 2009, p. 5389-5399, Vol. 77, No. 12
0019-9567/09/$08.00+0 doi:10.1128/IAI.00809-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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