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

16 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 1 2016

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of 'Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming'. Together they form a unique fingerprint.

  • Cite this