Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming

Annmarie Torres, Joanna D. Luke, Amy L. Kullas, Kanishk Kapilashrami, Yair M. Botbol, Antonius Koller, Peter J. Tonge, Emily I. Chen, Fernando Macian-Juan, Adrianus W M van der Velden

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Salmonellae are pathogenic bacteria that induce immunosuppression by mechanisms that remain largely unknown. Previously, we showed that a putative type II L-asparaginase produced by Salmonella Typhimurium inhibits T cell responses and mediates virulence in a murine model of infection. Here, we report that this putative L-asparaginase exhibits L-asparagine hydrolase activity required for Salmonella Typhimurium to inhibit T cells. We show that L-asparagine is a nutrient important for T cell activation and that L-asparagine deprivation, such as that mediated by the Salmonella Typhimurium L-asparaginase, causes suppression of activation-induced mammalian target of rapamycin signaling, autophagy, Myc expression, and L-lactate secretion. We also show that L-asparagine deprivation mediated by the Salmonella Typhimurium L-asparaginase causes suppression of cellular processes and pathways involved in protein synthesis, metabolism, and immune response. Our results advance knowledge of a mechanism used by Salmonella Typhimurium to inhibit T cell responses and mediate virulence, and provide new insights into the prerequisites of T cell activation. We propose a model in which L-asparagine deprivation inhibits T cell exit from quiescence by causing suppression of activation-induced metabolic reprogramming.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalJournal of Leukocyte Biology
Volume99
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Asparaginase
Asparagine
Salmonella
Salmonella typhimurium
T-Lymphocytes
Virulence
Autophagy
Hydrolases
Sirolimus
Immunosuppression
Cellular Reprogramming
Lactic Acid
Bacteria
Food
Infection
Proteins

Keywords

  • Bacteria
  • Host
  • Inhibition
  • Pathogen
  • T-lymphocyte

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming. / Torres, Annmarie; Luke, Joanna D.; Kullas, Amy L.; Kapilashrami, Kanishk; Botbol, Yair M.; Koller, Antonius; Tonge, Peter J.; Chen, Emily I.; Macian-Juan, Fernando; van der Velden, Adrianus W M.

In: Journal of Leukocyte Biology, Vol. 99, No. 2, 01.02.2016, p. 387-398.

Research output: Contribution to journalArticle

Torres, Annmarie ; Luke, Joanna D. ; Kullas, Amy L. ; Kapilashrami, Kanishk ; Botbol, Yair M. ; Koller, Antonius ; Tonge, Peter J. ; Chen, Emily I. ; Macian-Juan, Fernando ; van der Velden, Adrianus W M. / Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming. In: Journal of Leukocyte Biology. 2016 ; Vol. 99, No. 2. pp. 387-398.
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