L-asparaginase II produced by Salmonella typhimurium inhibits T cell responses and mediates virulence. Academic Article uri icon

abstract

  • Salmonella enterica serovar Typhimurium avoids clearance by the host immune system by suppressing Tcell responses; however, the mechanisms that mediate this immunosuppression remain unknown. We show that S. Typhimurium inhibit Tcell responses by producing L-Asparaginase II, which catalyzes the hydrolysis of L-asparagine to aspartic acid and ammonia. L-Asparaginase II is necessary and sufficient to suppress Tcell blastogenesis, cytokine production, and proliferation and to downmodulate expression of the Tcell receptor. Furthermore, S.Typhimurium-induced inhibition ofTcells invitro is prevented upon addition of L-asparagine. S.Typhimurium lacking the L-Asparaginase II gene (STM3106) are unable to inhibit Tcell responses and exhibit attenuated virulence invivo. L-Asparaginases are used to treat acute lymphoblastic leukemia through mechanisms that likely involve amino acid starvation of leukemic cells, andthese findings indicate that pathogens similarlyuse L-asparagine deprivation to limit Tcell responses.

published proceedings

  • Cell Host Microbe

altmetric score

  • 6

author list (cited authors)

  • Kullas, A. L., McClelland, M., Yang, H., Tam, J. W., Torres, A., Porwollik, S., ... van der Velden, A.

citation count

  • 66

complete list of authors

  • Kullas, Amy L||McClelland, Michael||Yang, Hee-Jeong||Tam, Jason W||Torres, AnnMarie||Porwollik, Steffen||Mena, Patricio||McPhee, Joseph B||Bogomolnaya, Lydia||Andrews-Polymenis, Helene||van der Velden, Adrianus WM

publication date

  • December 2012