Journal of Molecular Medicine

, Volume 91, Issue 10, pp 1199–1205

HIF-1α influences myeloid cell antigen presentation and response to subcutaneous OVA vaccination

Authors

  • Tamara Bhandari
    • Department of PediatricsUniversity of California San Diego
    • Biomedical Sciences Graduate ProgramUniversity of California San Diego
  • Joshua Olson
    • Department of PediatricsUniversity of California San Diego
  • Randall S. Johnson
    • Department of PediatricsUniversity of California San Diego
    • Department of Physiology, Development, and NeuroscienceUniversity of Cambridge
    • Department of PediatricsUniversity of California San Diego
    • Biomedical Sciences Graduate ProgramUniversity of California San Diego
    • Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of California San Diego
Original Article

DOI: 10.1007/s00109-013-1052-y

Cite this article as:
Bhandari, T., Olson, J., Johnson, R.S. et al. J Mol Med (2013) 91: 1199. doi:10.1007/s00109-013-1052-y

Abstract

Hypoxia-inducible factor (HIF)-1 is a transcription factor known to play an important role in regulating the innate immune response to infection. Under baseline conditions, cellular HIF-1 levels in leukocytes are scarce, but levels rise rapidly in response to hypoxia or molecular signals of infection or inflammation such as microbial surface molecules and host-derived cytokines. Innate immune cells such as macrophages, neutrophils, and mast cells exhibit increased microbicidal activity when HIF-1 levels are increased, and mice lacking HIF-1 are more susceptible to invasive bacterial infection. In this study, we used genetic and pharmacologic means to determine whether HIF-1 also plays an important role in the adaptive immune response to infection. HIF-1α/Tie-2 Cre+ mice harboring a >90 % knockdown of HIF-1 in myeloid cells were studied. We found antigen-presenting cells from these mice that expressed lower levels of MHC-II and the costimulatory molecules CD80 and CD86, and were less able to induce T cell proliferation. These differences were present at baseline and persisted after activation. Increasing HIF-1 levels in wild-type (WT) cells by using the prolyl hydroxylase inhibitor drug AKB-4924 had the opposite effect, increasing MHC and costimulatory molecule expression and T cell proliferation. In experimental vaccination, HIF-1α/Tie-2 Cre+ mice exhibited a weaker T cell response and lower antibody levels in response to vaccination than WT mice, while WT mice treated with a drug to elevate HIF-1 responded more strongly to vaccination. Thus, HIF-1 participates in bridging the innate and adaptive immune responses and may merit further exploration as an adjuvant target.

Keywords

Hypoxia-inducible factorDendritic cellAntigen presentationAdjuvantVaccination

Copyright information

© Springer-Verlag Berlin Heidelberg 2013