Utilization of Host Polyamines in Alternatively Activated Macrophages Promotes Chronic Infection by Brucella abortus.

摘要: Treatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course multiple drugs. A barrier to developing strategies that enhance efficacy against these is our poor understanding the nutritional environment maintains persistence. The pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAMs); however, knowledge metabolic adaptations promoting exploitation this niche limited. Here we show one mechanism enhanced survival AAMs shift macrophage arginine utilization from production nitric oxide (NO) biosynthesis polyamines, induced by interleukin 4 (IL-4)/IL-13 treatment. Production polyamines infected promoted both B. chronic infection mice, as inhibition polyamine synthesis or inactivation putative putrescine transporter encoded potIHGF reduced persistence mice. These results demonstrate increased availability arginase-1 expression IL-4/IL-13-induced promotes within suggest targeting pathway may aid eradicating infection.