Tissue Metabolic Changes Drive Cytokine Responses to Mycobacterium tuberculosis

Ekta Lachmandas, Ana B. Rios-Miguel, Valerie A.C.M. Koeken, Eva van der Pasch, Vinod Kumar, Vasiliki Matzaraki, Yang Li, Marije Oosting, Leo A.B. Joosten, Richard A. Notebaart, Mahdad Noursadeghi, Mihai G. Netea, Reinout van Crevel, Gabriele Pollara*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Cellular metabolism can influence host immune responses to Mycobacterium tuberculosis. Using a systems biology approach, differential expression of 292 metabolic genes involved in glycolysis, glutathione, pyrimidine, and inositol phosphate pathways was evident at the site of a human tuberculin skin test challenge in patients with active tuberculosis infection. For 28 metabolic genes, we identified single nucleotide polymorphisms that were trans-acting for in vitro cytokine responses to M. tuberculosis stimulation, including glutathione and pyrimidine metabolism genes that alter production of Th1 and Th17 cytokines. Our findings identify novel therapeutic targets in host metabolism that may shape protective immunity to tuberculosis.

Original languageEnglish
Pages (from-to)165-170
JournalJournal of Infectious Diseases
Volume218
Issue number1
DOIs
Publication statusPublished - 5 Jun 2018

Keywords

  • cytokines
  • functional genomics
  • human challenge model
  • immune response
  • immunometabolism
  • metabolism
  • microarrays
  • transcriptomics
  • tuberculosis

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    Lachmandas, E., Rios-Miguel, A. B., Koeken, V. A. C. M., van der Pasch, E., Kumar, V., Matzaraki, V., ... Pollara, G. (2018). Tissue Metabolic Changes Drive Cytokine Responses to Mycobacterium tuberculosis. Journal of Infectious Diseases, 218(1), 165-170. https://doi.org/10.1093/infdis/jiy173