HLA-DRB1 alleles control allergic bronchopulmonary aspergillosis-like pulmonary responses in humanized transgenic mice

Sherri Koehm, Raymond G. Slavin, Patricia S. Hutcheson, Theodore Trejo, Chella S. David, Clifford J. Bellone

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a lung hypersensitivity disease mediated in part by CD4+ TH2 cells. There is a significant association between ABPA and the HLA-DR2 genotypes DRB1*1501 and DRB1*1503, whereas resistance might be associated with HLA-DRB1*1502. Objective: We sought to elucidate the role of HLA-DR alleles in allergic inflammation in lungs. Methods: HLA-DR humanized transgenic mice expressing either the susceptible or resistant alleles were analyzed for the nature and extent of pulmonary inflammation after exposure to Aspergillus species antigens. Results: Exposed DRB1*1501 and DRB1*1503 transgenic mice displayed infiltrates made up prominently of eosinophils, which is consistent with the inflammation found in ABPA. The resistant DRB1*1502 mice, on the other hand, displayed minimal to moderate inflammation, consisting mainly of T-cell infiltrates. Significantly more mucin was produced in the DRB1*1503 and DRB1*1501 mice, and their ability to limit the number of Aspergillus species conidia within the lung parenchyma was impaired. Despite their differences, both the DRB1*1503 and DRB1*1502 strains mounted comparable T cell-proliferative responses to Aspergillus species antigens. Conclusion: The HLA-DR2 alleles DRB1*1501 and DRB1*1503 play a major role in the development of allergic pulmonary inflammation. In contrast, the HLA-DR2 allele DRB1*1502 mediates a nonallergic TH1-like response to the organism, possibly explaining an ABPA resistance factor. These results are in support of our published human studies in patients with cystic fibrosis and asthma. Clinical implications: HLA-DR typing in patients with cystic fibrosis and asthma will aid in the identification of individuals at risk for ABPA.

Original languageEnglish (US)
Pages (from-to)570-577
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number3
DOIs
StatePublished - Sep 1 2007

Keywords

  • Allergic bronchopulmonary aspergillosis
  • Aspergillus fumigatus
  • HLA-DR
  • MHC
  • T2
  • asthma
  • cystic fibrosis
  • eosinophilia
  • pulmonary immunity
  • transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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