Short-term IL-15 priming leaves a long-lasting signalling imprint in mouse NK cells independently of a metabolic switch

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Abstract
Zinc is one of the most important trace elements for life and its deficiency, like its excess, can be fatal. In the bacterial opportunistic pathogen Pseudomonas aeruginosa, Zn homeostasis is not only required for survival, but also for virulence and antibiotic resistance. Thus, the bacterium possesses multiple Zn import/export/storage systems. In this work, we determine the expression dynamics of the entire P. aeruginosa Zn homeostasis network at both transcript and protein levels. Precisely, we followed the switch from a Zn-deficient environment, mimicking the initial immune strategy to bacterial infections, to a Zn-rich environment, representing the phagocyte metal boost used to eliminate an engulfed pathogen. Thanks to the use of the NanoString technology, we timed the global silencing of Zn import systems and the orchestrated induction of Zn export systems. We show that the induction of Zn export systems is hierarchically organized as a function of their impact on Zn homeostasis. Moreover, we identify PA2807 as a novel Zn resistance component in P. aeruginosa and highlight new regulatory links among Zn-homeostasis systems. Altogether, this work unveils a sophisticated and adaptative homeostasis network, which complexity is key in determining a pathogen spread in the environment and during host-colonization.
Funding Information
  • Swedish Research Council
  • Swedish Cancer Society
  • Region Stockholm
  • Radiumhemmets Forskningsfonder
  • Aroseniusfonden and Karolinska Institutet
  • Karolinska Institutet
  • Karolinska Institutet (KID grants)
  • Swiss National Science Foundation (P400PM_183909)

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