Oxidized PUFAs Increase Susceptibility of Mice to Salmonella Infection by Diminishing Host's Innate Immune Responses.

Dietary ω-3 PUFAs are highly prone to oxidation, and this may potentially limit their application in the health-promoting field. Here, we sought to investigate whether and how oxidized PUFAs modulate the susceptibility of mice to Salmonella typhimurium ( S . Tm) infection. Algae oil (AO) and oxidized algae oil (ox-AO) were administered to the C57BL/6 mice prior to S . Tm infection. Compared to the S . Tm group, ox-AO increased bacterial burden in systemic and intestinal tissues, downregulated host anti-infection responses, and developed worse colitis. In macrophages, ox-AO decreased both phagocytosis of S . Tm and clearance of intracellular bacteria and dampened the activation of mitogen-activated protein kinase (MAPK), NF-κB, and autophagy pathways. Furthermore, ox-AO diminished LPS-induced inflammatory cytokine production and S . Tm induced NLRC4 inflammasome activation. This study reveals that oxidized PUFAs may contribute to the development of enteric infections and regular monitoring of the oxidation status in commercial PUFA supplements to prevent their potential adverse impact on human health.