n-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Cambridge University Press
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-3þ and n-3FAD/n-3þ) 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), CD4þ 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.
Description
Research Article
Keywords
Host-directed therapy, Inflammation, n-3 long-chain PUFA, Tuberculosis