PMID- 19752036 OWN - NLM STAT- MEDLINE DCOM- 20091204 LR - 20211020 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 77 IP - 12 DP - 2009 Dec TI - Th2 but not Th1 immune bias results in altered lung functions in a murine model of pulmonary Cryptococcus neoformans infection. PG - 5389-99 LID - 10.1128/IAI.00809-09 [doi] AB - 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. FAU - Jain, Aditya V AU - Jain AV AD - Department of Veteran's Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan 48105, USA. FAU - Zhang, Yanmei AU - Zhang Y FAU - Fields, W Bradley AU - Fields WB FAU - McNamara, David A AU - McNamara DA FAU - Choe, Mun Y AU - Choe MY FAU - Chen, Gwo-Hsiao AU - Chen GH FAU - Erb-Downward, John AU - Erb-Downward J FAU - Osterholzer, John J AU - Osterholzer JJ FAU - Toews, Galen B AU - Toews GB FAU - Huffnagle, Gary B AU - Huffnagle GB FAU - Olszewski, Michal A AU - Olszewski MA LA - eng GR - R01 AI059201/AI/NIAID NIH HHS/United States GR - R01 HL051082/HL/NHLBI NIH HHS/United States GR - R01-HL51082/HL/NHLBI NIH HHS/United States GR - R01-AI-059201/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20090914 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Inflammation Mediators) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Animals MH - Brain/microbiology MH - Colony Count, Microbial MH - Cryptococcosis/*immunology/pathology MH - Cryptococcus neoformans/*immunology MH - Female MH - Immunoglobulin E/blood MH - Inflammation/pathology MH - Inflammation Mediators/analysis MH - Leukocytes/immunology MH - Lung/chemistry/microbiology/*pathology/*physiopathology MH - Lung Diseases, Fungal/*immunology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Rats MH - Respiratory Function Tests MH - Th1 Cells/*immunology MH - Th2 Cells/*immunology PMC - PMC2786439 EDAT- 2009/09/16 06:00 MHDA- 2009/12/16 06:00 PMCR- 2010/06/01 CRDT- 2009/09/16 06:00 PHST- 2009/09/16 06:00 [entrez] PHST- 2009/09/16 06:00 [pubmed] PHST- 2009/12/16 06:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - IAI.00809-09 [pii] AID - 0809-09 [pii] AID - 10.1128/IAI.00809-09 [doi] PST - ppublish SO - Infect Immun. 2009 Dec;77(12):5389-99. doi: 10.1128/IAI.00809-09. Epub 2009 Sep 14.