The blood transcriptome of experimental melioidosis reflects disease severity and shows considerable similarity with the human disease

Laura Conejero, Krzysztof Potempa, Christine M. Graham, Natasha Spink, Simon Blankley, Francisco J. Salguero, Rungnapa Pankla-Sranujit, Prasong Khaenam, Jacques F. Banchereau, Virginia Pascual, Damien J. Chaussabel, Ganjana Lertmemongkolchai, Anne O'Garra, Gregory J. Bancroft

Research output: Contribution to journalArticle

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Abstract

Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. In this study, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic, or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL-10, TREM1, and IFN signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodeling, including matrix metalloproteases and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-γ, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL-10, TREM1, and IFN signaling, revealing the common immune response occurring in both mice and humans.

Original languageEnglish
Pages (from-to)3248-3261
Number of pages14
JournalJournal of Immunology
Volume195
Issue number7
DOIs
Publication statusPublished - 1 Oct 2015
Externally publishedYes

Fingerprint

Melioidosis
Transcriptome
Burkholderia pseudomallei
Arginase
Infection
Interleukin-10
Active Immunotherapy
Metalloproteases
Innate Immunity
Genes
Sepsis
Fibrosis
Chronic Disease
Up-Regulation
Collagen
Immunohistochemistry
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

Conejero, L., Potempa, K., Graham, C. M., Spink, N., Blankley, S., Salguero, F. J., ... Bancroft, G. J. (2015). The blood transcriptome of experimental melioidosis reflects disease severity and shows considerable similarity with the human disease. Journal of Immunology, 195(7), 3248-3261. https://doi.org/10.4049/jimmunol.1500641

The blood transcriptome of experimental melioidosis reflects disease severity and shows considerable similarity with the human disease. / Conejero, Laura; Potempa, Krzysztof; Graham, Christine M.; Spink, Natasha; Blankley, Simon; Salguero, Francisco J.; Pankla-Sranujit, Rungnapa; Khaenam, Prasong; Banchereau, Jacques F.; Pascual, Virginia; Chaussabel, Damien J.; Lertmemongkolchai, Ganjana; O'Garra, Anne; Bancroft, Gregory J.

In: Journal of Immunology, Vol. 195, No. 7, 01.10.2015, p. 3248-3261.

Research output: Contribution to journalArticle

Conejero, L, Potempa, K, Graham, CM, Spink, N, Blankley, S, Salguero, FJ, Pankla-Sranujit, R, Khaenam, P, Banchereau, JF, Pascual, V, Chaussabel, DJ, Lertmemongkolchai, G, O'Garra, A & Bancroft, GJ 2015, 'The blood transcriptome of experimental melioidosis reflects disease severity and shows considerable similarity with the human disease', Journal of Immunology, vol. 195, no. 7, pp. 3248-3261. https://doi.org/10.4049/jimmunol.1500641
Conejero, Laura ; Potempa, Krzysztof ; Graham, Christine M. ; Spink, Natasha ; Blankley, Simon ; Salguero, Francisco J. ; Pankla-Sranujit, Rungnapa ; Khaenam, Prasong ; Banchereau, Jacques F. ; Pascual, Virginia ; Chaussabel, Damien J. ; Lertmemongkolchai, Ganjana ; O'Garra, Anne ; Bancroft, Gregory J. / The blood transcriptome of experimental melioidosis reflects disease severity and shows considerable similarity with the human disease. In: Journal of Immunology. 2015 ; Vol. 195, No. 7. pp. 3248-3261.
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