Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice

Nathan W Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B Kennedy, Gregory A. Poland, Michael A Barry, Karl A Nath, Andrew David Badley

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral- based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median survival 5.5 vs. 6.5 d, P=0.016). HO-1-deficient mice had impaired production of antibody following influenza vaccination compared to WT mice (mean antibody titer 869 vs. 1698, P=0.02). One SNP in HO-1 and one SNP in the constitutively expressed isoform HO-2 were independently associated with decreased antibody production after influenza vaccination in healthy human volunteers (P=0.017 and 0.014, respectively). HO-1 deficient mice were paired with sex- and age-matched WT controls. HO-1 affects the immune response to both influenza infection and vaccination, suggesting that therapeutic induction of HO-1 expression may represent a novel adjuvant to enhance influenza vaccine effectiveness.

Original languageEnglish (US)
Pages (from-to)2911-2918
Number of pages8
JournalFASEB Journal
Volume26
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Heme Oxygenase-1
Virus Diseases
Orthomyxoviridae
Viruses
Vaccination
Human Influenza
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Influenza Vaccines
Infection
Antibody Formation
Antibodies
Genes
Chordata
Survival
Genome-Wide Association Study
Influenza A virus
Healthy Volunteers
Protein Isoforms

Keywords

  • Cytokine
  • Pathogenesis
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice. / Cummins, Nathan W; Weaver, Eric A.; May, Shannon M.; Croatt, Anthony J.; Foreman, Oded; Kennedy, Richard B; Poland, Gregory A.; Barry, Michael A; Nath, Karl A; Badley, Andrew David.

In: FASEB Journal, Vol. 26, No. 7, 07.2012, p. 2911-2918.

Research output: Contribution to journalArticle

Cummins, Nathan W ; Weaver, Eric A. ; May, Shannon M. ; Croatt, Anthony J. ; Foreman, Oded ; Kennedy, Richard B ; Poland, Gregory A. ; Barry, Michael A ; Nath, Karl A ; Badley, Andrew David. / Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice. In: FASEB Journal. 2012 ; Vol. 26, No. 7. pp. 2911-2918.
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