Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator

Jenna B. Allard, Matthew E. Poynter, Kieren Marr, Lauren Cohn, Mercedes Rincon, Laurie A. Whittaker

Research output: Contribution to journalArticle

Abstract

Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20-40% of CF patients and are of unclear clinical significance. In this study, we demonstrate that CF transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftr tm1Unc- TgN(fatty acid-binding protein)CFTR) and mutant (ΔF508) mice develop profound long inflammation in response to Aspergillus fumigatus hyphal Ag exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in serum. In contrast, CFTR deficiency does not promote a Th1 immune response. Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)5186-5194
Number of pages9
JournalJournal of Immunology
Volume177
Issue number8
StatePublished - Oct 15 2006
Externally publishedYes

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Cystic Fibrosis Transmembrane Conductance Regulator
Aspergillus fumigatus
T-Lymphocytes
Cystic Fibrosis
Interleukin-4
Th1-Th2 Balance
Inflammation
Fatty Acid-Binding Proteins
Aspergillus
Respiratory Insufficiency
Immunoglobulin E
Lung Diseases
Ligation
Immunoglobulin G
Lung
Infection
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator. / Allard, Jenna B.; Poynter, Matthew E.; Marr, Kieren; Cohn, Lauren; Rincon, Mercedes; Whittaker, Laurie A.

In: Journal of Immunology, Vol. 177, No. 8, 15.10.2006, p. 5186-5194.

Research output: Contribution to journalArticle

Allard, Jenna B. ; Poynter, Matthew E. ; Marr, Kieren ; Cohn, Lauren ; Rincon, Mercedes ; Whittaker, Laurie A. / Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator. In: Journal of Immunology. 2006 ; Vol. 177, No. 8. pp. 5186-5194.
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