Burkholderia pseudomallei proteins presented by monocyte-derived dendritic cells stimulate human memory T cells in vitro

Patcharaporn Tippayawat, Maneerat Pinsiri, Darawan Rinchai, Donporn Riyapa, Amornrat Romphruk, Yunn Hwen Gan, Raymond L. Houghton, Philip L. Felgner, Richard W. Titball, Mark P. Stevens, Edouard E. Galyov, Gregory J. Bancroft, Ganjana Lertmemongkolchai

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18 Citations (Scopus)

Abstract

Melioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogen Burkholderia pseudomallei. The disease is endemic in Southeast Asia and Northern Australia, and no effective vaccine exists. To describe human cell-mediated immune responses to B. pseudomallei and to identify candidate antigens for vaccine development, the ability of antigen-pulsed monocyte-derived dendritic cells (moDCs) to trigger autologous T-cell responses to B. pseudomallei and its products was tested. moDCs were prepared from healthy individuals exposed or not exposed to B. pseudomallei, based on serological evidence. These were pulsed with heat-killed B. pseudomallei or purified antigens, including ABC transporters (LolC, OppA, and PotF), Bsa type III secreted proteins (BipD and BopE), tandem repeat sequence-containing proteins (Rp1 and Rp2), flagellin, and heat shock proteins (Hsp60 and Hsp70), prior to being mixed with autologous T-cell populations. After pulsing of cells with either heat-killed B. pseudomallei, LolC, or Rp2, coculturing the antigen-pulsed moDCs with T cells elicited gamma interferon production from CD4+ T cells from seropositive donors at levels greater than those for seronegative donors. These antigens also induced granzyme B (cytotoxic) responses from CD8+ T cells. Activation of antigen-specific CD4+ T cells required direct contact with moDCs and was therefore not dependent on soluble mediators. Rp peptide epitopes recognized by T cells in healthy individuals were identified. Our study provides valuable novel data on the induction of human cell-mediated immune responses to B. pseudomallei and its protein antigens that may be exploited in the rational development of vaccines to combat melioidosis.

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalInfection and Immunity
Volume79
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Tippayawat, P., Pinsiri, M., Rinchai, D., Riyapa, D., Romphruk, A., Gan, Y. H., Houghton, R. L., Felgner, P. L., Titball, R. W., Stevens, M. P., Galyov, E. E., Bancroft, G. J., & Lertmemongkolchai, G. (2011). Burkholderia pseudomallei proteins presented by monocyte-derived dendritic cells stimulate human memory T cells in vitro. Infection and Immunity, 79(1), 305-313. https://doi.org/10.1128/IAI.00803-10