Th2 but not Th1 immune bias results in altered lung functions in a murine model of pulmonary Cryptococcus neoformans infection.
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.
Jain
Aditya V
AV
Department of Veteran's Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan 48105, USA.
Zhang
Yanmei
Y
Fields
W Bradley
WB
McNamara
David A
DA
Choe
Mun Y
MY
Chen
Gwo-Hsiao
GH
Erb-Downward
John
J
Osterholzer
John J
JJ
Toews
Galen B
GB
Huffnagle
Gary B
GB
Olszewski
Michal A
MA
D000818:Animals; D001921:Brain / Q000382:microbiology; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000276:immunology* / Q000473:pathology; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000032:analysis; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology*; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D012129:Respiratory Function Tests; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018836:Inflammation Mediators; D007073:Immunoglobulin E