Document Detail


Repeated exposure to Aspergillus fumigatus conidia results in CD4+ T cell-dependent and -independent pulmonary arterial remodeling in a mixed Th1/Th2/Th17 microenvironment that requires interleukin-4 (IL-4) and IL-10.
MedLine Citation:
PMID:  22064716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary arterial remodeling is a pathological process seen in a number of clinical disease states, driven by inflammatory cells and mediators in the remodeled artery microenvironment. In murine models, Th2 cell-mediated immune responses to inhaled antigens, such as purified Aspergillus allergen, have been reported to induce remodeling of pulmonary arteries. We have previously shown that repeated intranasal exposure of healthy C57BL/6 mice to viable, resting Aspergillus fumigatus conidia leads to the development of chronic pulmonary inflammation and the coevolution of Th1, Th2, and Th17 responses in the lungs. Our objective was to determine whether repeated intranasal exposure to Aspergillus conidia would induce pulmonary arterial remodeling in this mixed Th inflammatory microenvironment. Using weekly intranasal conidial challenges, mice developed robust pulmonary arterial remodeling after eight exposures (but not after two or four). The process was partially mediated by CD4+ T cells and by interleukin-4 (IL-4) production, did not require eosinophils, and was independent of gamma interferon (IFN-γ) and IL-17. Furthermore, remodeling could occur even in the presence of strong Th1 and Th17 responses. Rather than serving an anti-inflammatory function, IL-10 was required for the development of the Th2 response to A. fumigatus conidia. However, in contrast to previous studies of pulmonary arterial remodeling driven by the A. fumigatus allergen, viable conidia also stimulated pulmonary arterial remodeling in the absence of CD4+ T cells. Remodeling was completely abrogated in IL-10-/- mice, suggesting that a second, CD4+ T cell-independent, IL-10-dependent pathway was also driving pulmonary arterial remodeling in response to repeated conidial exposure.
Authors:
Andrew B Shreiner; Benjamin J Murdock; Amir A Sadighi Akha; Nicole R Falkowski; Paul J Christensen; Eric S White; Cory M Hogaboam; Gary B Huffnagle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-07
Journal Detail:
Title:  Infection and immunity     Volume:  80     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-26     Completed Date:  2012-02-16     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  388-97     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspergillus fumigatus / immunology,  pathogenicity*
CD4-Positive T-Lymphocytes / immunology*
Inhalation Exposure
Interleukin-10 / immunology*
Interleukin-4 / immunology*
Lung / immunology,  microbiology*,  pathology*
Mice
Mice, Inbred C57BL
Neovascularization, Pathologic*
Spores, Fungal / immunology,  pathogenicity
Th1 Cells / immunology
Th17 Cells / immunology
Th2 Cells / immunology
Grant Support
ID/Acronym/Agency:
R01AI064479/AI/NIAID NIH HHS; R21AI083473/AI/NIAID NIH HHS; R21AI087869/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/IL10 protein, mouse; 130068-27-8/Interleukin-10; 207137-56-2/Interleukin-4
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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