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 Botbol, Antonius Koller, Peter J. Tonge, Emily I. Chen, Fernando Macian, Adrianus W.M. van der Velden

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 2016

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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