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Nutrients. 2019 Sep 6;11(9). pii: E2137. doi: 10.3390/nu11092137.

Omega-3 Polyunsaturated Fatty Acids Prevent Toxoplasma gondii Infection by Inducing Autophagy via AMPK Activation.

Choi JW1,2,3, Lee J1,2,3, Lee JH1,2,3, Park BJ1,2,3, Lee EJ1,2,3, Shin S4, Cha GH1,2, Lee YH1,2, Lim K5, Yuk JM6,7,8.

Author information

1
Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
2
Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
3
Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
4
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
5
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Korea. yjaemin0@cnu.ac.kr.
6
Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. kyulim@cnu.ac.kr.
7
Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. kyulim@cnu.ac.kr.
8
Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. kyulim@cnu.ac.kr.

Abstract

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have potential protective activity in a variety of infectious diseases, but their actions and underlying mechanisms in Toxoplasma gondii infection remain poorly understood. Here, we report that docosahexaenoic acid (DHA) robustly induced autophagy in murine bone marrow-derived macrophages (BMDMs). Treatment of T. gondii-infected macrophages with DHA resulted in colocalization of Toxoplasma parasitophorous vacuoles with autophagosomes and reduced intracellular survival of T. gondii. The autophagic and anti-Toxoplasma effects induced by DHA were mediated by AMP-activated protein kinase (AMPK) signaling. Importantly, BMDMs isolated from Fat-1 transgenic mice, a well-known animal model capable of synthesizing ω3-PUFAs from ω6-PUFAs, showed increased activation of autophagy and AMPK, leading to reduced intracellular survival of T. gondii when compared with wild-type BMDMs. Moreover, Fat-1 transgenic mice exhibited lower cyst burden in the brain following infection with the avirulent strain ME49 than wild-type mice. Collectively, our results revealed mechanisms by which endogenous ω3-PUFAs and DHA control T. gondii infection and suggest that ω3-PUFAs might serve as therapeutic candidate to prevent toxoplasmosis and infection with other intracellular protozoan parasites.

KEYWORDS:

AMP-activated protein kinase; Autophagy; Bone marrow-derived macrophages; Fat-1 transgenic mice; Omega 3 polyunsaturated fatty acid; Toxoplasma gondii

PMID:
31500218
DOI:
10.3390/nu11092137
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