N-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status

Arista Nienaber, Mumin Ozturk, Robin Dolman, Renee Blaauw, Lizelle L. Zandberg, Simone Van Rensburg, Melinda Britz, Frank E.A. Hayford, Frank Brombacher, Du Toit Loots, Cornelius M. Smuts, Suraj P. Parihar, Linda Malan

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-Two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or-deficient (n-3FAD) diet for 6 weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n-3FAD/n-3+) or continued on n-3FAS or n-3FAD diets for 3 weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P = 0·003), T cells (P = 0·019), CD4+ T cells (P = 0·014) and interferon (IFN)-γ (P < 0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P = 0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1β and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided 1 week after infection in the context of a sufficient n-3 PUFA status, whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.

Original languageEnglish
Pages (from-to)384-397
Number of pages14
JournalBritish Journal of Nutrition
Volume127
Issue number3
DOIs
Publication statusPublished - 14 Feb 2022

Keywords

  • Host-directed therapy
  • Inflammation
  • Tuberculosis
  • n-3 long-chain PUFA

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