Skip to content

Research at St Andrews

T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei: a correlate of disease outcome in acute melioidosis

Research output: Contribution to journalArticle

Author(s)

Catherine Reynolds, Amélie Goudet, Kemajittra Jenjaroen, Manutsanun Sumonwiriya, Darawan Rinchai, Julie Musson, Saskia Overbeek, Julia Makinde, Kathryn Quigley, Jiten Manji, Natasha Spink, Pagnarith Yos, Vanaporn Wuthiekanun, Gregory Bancroft, John Robinson, Ganjana Lertmemongkolchai, Susanna Dunachie, Bernard Maillere, Matthew Holden, Daniel Altmann & 1 others Rosemary Boyton

School/Research organisations

Abstract

There is an urgent need for a better understanding of adaptive immunity to Burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in Southeast Asia and Northern Australia. The imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. In several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to host oxidative stress, and they can stimulate strong adaptive immunity. We show that alkyl hydroperoxidase reductase (AhpC) of B. pseudomallei is strongly immunogenic for T cells of 'humanized' HLA transgenic mice and seropositive human donors. Some T cell epitopes, such as p6, are able to bind diverse HLA class II heterodimers and stimulate strong T cell immunity in mice and humans. Importantly, patients with acute melioidosis who survive infection show stronger T cell responses to AhpC relative to those who do not. Although the sequence of AhpC is virtually invariant among global B. pseudomallei clinical isolates, a Cambodian isolate varies only in C-terminal truncation of the p6 T cell epitope, raising the possibility of selection by host immunity. This variant peptide is virtually unable to stimulate T cell immunity. For an infection in which there has been debate about centrality of T cell immunity in defense, these observations support a role for T cell immunity to AhpC in disease protection.
Close

Details

Original languageEnglish
Pages (from-to)4814-4824
Number of pages11
JournalThe Journal of Immunology
Volume194
Issue number10
DOIs
Publication statusPublished - 15 May 2015

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus

    Harrison, E. M., Ba, X., Coll, F., Blane, B., Restif, O., Carvell, H., Köser, C. U., Jamrozy, D., Reuter, S., Lovering, A., Gleadall, N., Bellis, K. L., Uhlemann, A. C., Lowy, F. D., Massey, R. C., Grilo, I. R., Sobral, R., Larsen, J., Rhod Larsen, A., Vingsbo Lundberg, C. & 5 othersParkhill, J., Paterson, G. K., Holden, M. T. G., Peacock, S. J. & Holmes, M. A., 24 Jun 2019, In : Nature Microbiology. 15 p.

    Research output: Contribution to journalArticle

  2. Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

    Davies, M. R., McIntyre, L., Mutreja, A., Lacey, J. A., Lees, J. A., Towers, R. J., Duchêne, S., Smeesters, P. R., Frost, H. R., Price, D. J., Holden, M. T. G., David, S., Giffard, P. M., Worthing, K. A., Seale, A. C., Berkley, J. A., Harris, S. R., Rivera-Hernandez, T., Berking, O., Cork, A. J. & 18 othersTorres, R. S. L. A., Lithgow, T., Strugnell, R. A., Bergmann, R., Nitsche-Schmitz, P., Chhatwal, G. S., Bentley, S. D., Fraser, J. D., Moreland, N. J., Carapetis, J. R., Steer, A. C., Parkhill, J., Saul, A., Williamson, D. A., Currie, B. J., Tong, S. Y. C., Dougan, G. & Walker, M. J., Jun 2019, In : Nature Genetics. 51, 6, p. 1035-1043

    Research output: Contribution to journalArticle

  3. Antimicrobial resistance in atopic dermatitis: need for an urgent rethink

    Harkins, C. P., Holden, M. T. G. & Irvine, A. D., Mar 2019, In : Annals of Allergy Asthma & Immunology. 122, 3, p. 236-240 5 p.

    Research output: Contribution to journalArticle

  4. Molecular epidemiology and expression of capsular polysaccharides in Staphylococcus aureus clinical isolates in the United States

    Mohamed, N., Timofeyeva, Y., Jamrozy, D., Rojas, E., Hao, L., Silmon de Monerri, N. C., Hawkins, J., Singh, G., Cai, B., Liberator, P., Sebastian, S., Donald, R. G. K., Scully, I. L., Jones, C. H., Creech, C. B., Thomsen, I., Parkhill, J., Peacock, S. J., Jansen, K. U., Holden, M. T. G. & 1 othersAnderson, A. S., 14 Jan 2019, In : PLoS ONE. 14, 1, 33 p., e0208356.

    Research output: Contribution to journalArticle

Related by journal

  1. ATP evokes Ca2+ responses and CXCL5 secretion via P2X4 receptor activation in human monocyte-derived macrophages

    Layhadi, J. A., Turner, J., Crossman, D. & Fountain, S. J., 1 Feb 2018, In : The Journal of Immunology. 200, 3, p. 1159-1168

    Research output: Contribution to journalArticle

  2. Evolution and Survival of Marine Carnivores Did Not Require a Diversity of Killer Cell Ig-Like Receptors or Ly49 NK Cell Receptors

    Hammond, J. A., Guethlein, L. A., Abi-Rached, L., Moesta, A. K. & Parham, P., 15 Mar 2009, In : The Journal of Immunology. 182, 6, p. 3618-3627 10 p.

    Research output: Contribution to journalArticle

  3. Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish

    Wang, T., Bird, S., Koussounadis, A., Holland, J. W., Carrington, A., Zou, J. & Secombes, C. J., 15 Jul 2009, In : The Journal of Immunology. 183, 2, p. 962-974 13 p.

    Research output: Contribution to journalArticle

  4. Novel MHC Class I Structures on Exosomes

    Lynch, S. J., Santos, S. G., Campbell, E. C., Nimmo, A. M. S., Botting, C. H., Prescott, A., Antoniou, A. N. & Powis, S. J., 1 Aug 2009, In : The Journal of Immunology. 183, 3, p. 1884-1891 8 p.

    Research output: Contribution to journalArticle

ID: 188980927