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

[摘要] Salmonellaearepathogenicbacteriathatinduceimmunosuppressionbymechanismsthatremainlargelyunknown.Previously,weshowedthataputativetypeIIl‐asparaginaseproducedbySalmonellaTyphimuriuminhibitsTcellresponsesandmediatesvirulenceinamurinemodelofinfection.Here,wereportthatthisputativel‐asparaginaseexhibitsl‐asparaginehydrolaseactivityrequiredforSalmonellaTyphimuriumtoinhibitTcells.Weshowthatl‐asparagineisanutrientimportantforTcellactivationandthatl‐asparaginedeprivation,suchasthatmediatedbytheSalmonellaTyphimuriuml‐asparaginase,causessuppressionofactivation‐inducedmammaliantargetofrapamycinsignaling,autophagy,Mycexpression,andl‐lactatesecretion.Wealsoshowthatl‐asparaginedeprivationmediatedbytheSalmonellaTyphimuriuml‐asparaginasecausessuppressionofcellularprocessesandpathwaysinvolvedinproteinsynthesis,metabolism,andimmuneresponse.OurresultsadvanceknowledgeofamechanismusedbySalmonellaTyphimuriumtoinhibitTcellresponsesandmediatevirulence,andprovidenewinsightsintotheprerequisitesofTcellactivation.Weproposeamodelinwhichl‐asparaginedeprivationinhibitsTcellexitfromquiescencebycausingsuppressionofactivation‐inducedmetabolicreprogramming...

[学科分类] 生理学

[关键词] host;pathogen;bacteria;inhibition;T‐lymphocyte