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


Tippayawat, P; Pinsiri, M; Rinchai, D; Riyapa, D; Romphruk, A; Gan, YH; Houghton, RL; Felgner, PL; Titball, RW; Stevens, MP; Galyov, EE; Bancroft, GJ; Lertmemongkolchai, G; (2010) Burkholderia pseudomallei proteins presented by monocyte-derived dendritic cells stimulate human memory T-cells in vitro. Infection and immunity. ISSN 0019-9567 DOI: 10.1128/IAI.00803-10

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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. MoDC 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 repeated sequence proteins (Rp1 and Rp2), flagellin and heat shock proteins (Hsp60 and Hsp70) prior to mixing with autologous T cell populations. After pulsing with either heat-killed B. pseudomallei or LolC or Rp2, co-culturing the antigen-pulsed moDC with T cells elicited interferon-gamma production of CD4(+) T cells from seropositive donors at levels greater than 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 moDC and is therefore not dependent on soluble mediators. Peptide epitopes of the Rp proteins 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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 21041491
Web of Science ID: 285550200030
URI: http://researchonline.lshtm.ac.uk/id/eprint/2194

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