| Coevolution of TH1, TH2, and TH17 responses during repeated pulmonary exposure to Aspergillus fumigatus conidia. | |
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MedLine Citation:
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PMID: 21041495 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aspergillus fumigatus, a ubiquitous airborne fungus, can cause invasive infection in immunocompromised individuals but also triggers allergic bronchopulmonary aspergillosis in a subset of otherwise healthy individuals repeatedly exposed to the organism. This study addresses a critical gap in our understanding of the immunoregulation in response to repeated exposure to A. fumigatus conidia. C57BL/6 mice were challenged intranasally with A. fumigatus conidia weekly, and leukocyte composition, activation, and cytokine production were examined after two, four, and eight challenges. Approximately 99% of A. fumigatus conidia were cleared within 24 h after inoculation, and repeated exposure to A. fumigatus conidia did not result in hyphal growth or accumulation of conidia with time. After 2 challenges, there was an early influx of neutrophils and regulatory T (T(reg)) cells into the lungs but minimal inflammation. Repeated exposure promoted sustained expansion of the draining lymph nodes, while the influx of eosinophils and other myeloid cells into the lungs peaked after four exposures and then decreased despite continued A. fumigatus challenges. Goblet cell metaplasia and low-level fibrosis were evident during the response. Repeated exposure to A. fumigatus conidia induced T cell activation in the lungs and the codevelopment by four exposures of T(H)1, T(H)2, and T(H)17 responses in the lungs, which were maintained through eight exposures. Changes in CD4 T cell polarization or T(reg) numbers did not account for the reduction in myeloid cell numbers later in the response, suggesting a non-T-cell regulatory pathway involved in dampening inflammation during repeated exposure to A. fumigatus conidia. |
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Authors:
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Benjamin J Murdock; Andrew B Shreiner; Roderick A McDonald; John J Osterholzer; Eric S White; Galen B Toews; Gary B Huffnagle |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-01 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-23 Completed Date: 2011-01-25 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 125-35 Citation Subset: IM |
Affiliation:
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Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-5642, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aspergillus fumigatus / immunology* CD4-Positive T-Lymphocytes Inflammation / immunology, pathology Lung / cytology Mice Mice, Inbred C57BL Pulmonary Aspergillosis / immunology* Spores, Fungal / immunology Th1 Cells / physiology* Th17 Cells / physiology* Th2 Cells / physiology* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL085083-04/HL/NHLBI NIH HHS; R01AI064479/AI/NIAID NIH HHS; R01HL085083/HL/NHLBI NIH HHS; R21AI083473-01/AI/NIAID NIH HHS; T32AI007413/AI/NIAID NIH HHS |
| Comments/Corrections | |
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