Utilization of host polyamines in alternatively activated macrophages promotes chronic infection by Brucella abortus

Tobias Kerrinnes, Maria G. Winter, Briana M. Young, Vladimir E. Diaz-Ochoa, Sebastian E. Winter, Renée M. Tsolis

Research output: Contribution to journalArticle

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Abstract

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

Original languageEnglish (US)
Article numbere00458-17
JournalInfection and Immunity
Volume86
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Brucella abortus
Polyamines
Macrophages
Infection
Interleukin-13
Interleukin-4
Anti-Bacterial Agents
Arginase
Putrescine
Arginine
Nitric Oxide
Pharmaceutical Preparations

Keywords

  • Nitrogen metabolism
  • Putrescine

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Utilization of host polyamines in alternatively activated macrophages promotes chronic infection by Brucella abortus. / Kerrinnes, Tobias; Winter, Maria G.; Young, Briana M.; Diaz-Ochoa, Vladimir E.; Winter, Sebastian E.; Tsolis, Renée M.

In: Infection and Immunity, Vol. 86, No. 3, e00458-17, 01.03.2018.

Research output: Contribution to journalArticle

Kerrinnes, Tobias ; Winter, Maria G. ; Young, Briana M. ; Diaz-Ochoa, Vladimir E. ; Winter, Sebastian E. ; Tsolis, Renée M. / Utilization of host polyamines in alternatively activated macrophages promotes chronic infection by Brucella abortus. In: Infection and Immunity. 2018 ; Vol. 86, No. 3.
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