Macrophages: Restriction of TCA Cycle Intermediates

Abstract

In hypoxic and excited tissues, oxygen (O2)- depen-gouge antimicrobial safeguards are disabled due to ashortage of O2. To acquire understanding into the mechanismsthat control bacterial disease under hypoxic condi-tions, we contaminated macrophages with the obligateintracellular pathogenCoxiella burnetii, the causativeagent of Q fever. Our investigations uncovered that hypoxia impededC. burnetiireplication in a hypoxia-inducible factor (HIF) 1asubordinate way. Mecha-nistically, under hypoxia, HIF1aimpaired the activityof STAT3, which thus diminished the intracellular levelof TCA cycle intermediates, including citrate, andimpededC. burnetiireplication in macrophages.However, bacterial reasonability was kept up, allowingthe tirelessness ofC. burnetii, which is a prerequisitefor the advancement of constant Q fever. This knowl-edge will open future examination roads on the way ogenesis of constant Q fever. Also, the regula-tion of TCA cycle metabolites by HIF1arepresentsa beforehand neglected component of host de-fense against intracellular microbes.