Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei

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Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei

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dc.contributor.author Tippayawat, Patcharaporn en_GB
dc.contributor.author Saenwongsa, Wipawee en_GB
dc.contributor.author Mahawantung, Jirawan en_GB
dc.contributor.author Suwannasaen, Duangchan en_GB
dc.contributor.author Chetchotisakd, Ploenchan en_GB
dc.contributor.author Limmathurotsakul, Direk en_GB
dc.contributor.author Peacock, Sharon J. en_GB
dc.contributor.author Felgner, Philip L. en_GB
dc.contributor.author Atkins, Helen S. en_GB
dc.contributor.author Titball, Richard W. en_GB
dc.contributor.author Bancroft, Gregory J. en_GB
dc.contributor.author Lertmemongkolchai, Ganjana en_GB
dc.date.accessioned 2010-06-10T15:26:24Z en_GB
dc.date.accessioned 2011-01-25T11:46:53Z en_US
dc.date.accessioned 2013-03-20T14:47:44Z
dc.date.issued 2009 en_GB
dc.description.abstract Background: Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-γ) is critical for resistance, but in humans the characteristics of IFN-γ production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined. Methods: Peripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-γ responses were analyzed by ELISPOT and flow cytometry. Findings: B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-γ. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4+ (and CD8+) T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector–memory (TEMRA) phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum. Conclusions: Individuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-γ that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide–conjugate subunit vaccines against this important but neglected disease. en_GB
dc.identifier.citation 3 (4), article 407 en_GB
dc.identifier.doi 10.1371/journal.pntd.0000407 en_GB
dc.identifier.uri http://hdl.handle.net/10036/104627 en_GB
dc.language.iso en en_GB
dc.publisher Public Library of Science en_GB
dc.relation.url http://dx.plos.org/10.1371/journal.pntd.0000407 en_GB
dc.relation.url http://dx.doi.org/10.1371/journal.pntd.0000407 en_GB
dc.title Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei en_GB
dc.type Article en_GB
dc.date.available 2010-06-10T15:26:24Z en_GB
dc.date.available 2011-01-25T11:46:53Z en_US
dc.date.available 2013-03-20T14:47:44Z
dc.identifier.issn 1935-2735 en_GB
dc.description Copyright: © 2009 Tippayawat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_GB
dc.identifier.journal PLoS Neglected Tropical Diseases en_GB


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