PMID- 31500218 OWN - NLM STAT- MEDLINE DCOM- 20200219 LR - 20200219 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 11 IP - 9 DP - 2019 Sep 6 TI - Omega-3 Polyunsaturated Fatty Acids Prevent Toxoplasma gondii Infection by Inducing Autophagy via AMPK Activation. LID - 10.3390/nu11092137 [doi] LID - 2137 AB - Omega-3 polyunsaturated fatty acids (omega3-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 omega3-PUFAs from omega6-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 omega3-PUFAs and DHA control T. gondii infection and suggest that omega3-PUFAs might serve as therapeutic candidate to prevent toxoplasmosis and infection with other intracellular protozoan parasites. FAU - Choi, Jae-Won AU - Choi JW AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lee, Jina AU - Lee J AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lee, Jae-Hyung AU - Lee JH AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Park, Byung-Joon AU - Park BJ AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lee, Eun Jin AU - Lee EJ AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Shin, Soyeon AU - Shin S AD - Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Cha, Guang-Ho AU - Cha GH AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lee, Young-Ha AU - Lee YH AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lim, Kyu AU - Lim K AD - Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon 35015, Korea. yjaemin0@cnu.ac.kr. FAU - Yuk, Jae-Min AU - Yuk JM AD - Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea. kyulim@cnu.ac.kr. AD - Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea. kyulim@cnu.ac.kr. AD - Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea. kyulim@cnu.ac.kr. LA - eng GR - NRF- 2017R1A6A3A1103057, NRF- 2017R1A5A2015385, and NRF-2018M2A2B3A02072069/National Research Foundation of Korea/ GR - reasearch fund/Chungnam National University/ PT - Journal Article DEP - 20190906 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Antiparasitic Agents) RN - 0 (Cadherins) RN - 25167-62-8 (Docosahexaenoic Acids) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Animals MH - Antiparasitic Agents/*pharmacology MH - Autophagy/*drug effects MH - Brain/drug effects/enzymology/parasitology/pathology MH - Cadherins/genetics/metabolism MH - Cell Line MH - Disease Models, Animal MH - Docosahexaenoic Acids/*pharmacology MH - Enzyme Activation MH - Humans MH - Macrophages/*drug effects/enzymology/parasitology MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Retinal Pigment Epithelium/drug effects/enzymology/parasitology MH - Signal Transduction MH - Toxoplasma/*drug effects/pathogenicity MH - Toxoplasmosis, Animal/enzymology/parasitology/pathology/*prevention & control MH - Toxoplasmosis, Cerebral/enzymology/parasitology/pathology/*prevention & control PMC - PMC6771136 OTO - NOTNLM OT - AMP-activated protein kinase OT - Autophagy OT - Bone marrow-derived macrophages OT - Fat-1 transgenic mice OT - Omega 3 polyunsaturated fatty acid OT - Toxoplasma gondii COIS- The authors declare no conflict of interest. EDAT- 2019/09/11 06:00 MHDA- 2020/02/20 06:00 PMCR- 2019/09/01 CRDT- 2019/09/11 06:00 PHST- 2019/07/18 00:00 [received] PHST- 2019/08/30 00:00 [revised] PHST- 2019/09/04 00:00 [accepted] PHST- 2019/09/11 06:00 [entrez] PHST- 2019/09/11 06:00 [pubmed] PHST- 2020/02/20 06:00 [medline] PHST- 2019/09/01 00:00 [pmc-release] AID - nu11092137 [pii] AID - nutrients-11-02137 [pii] AID - 10.3390/nu11092137 [doi] PST - epublish SO - Nutrients. 2019 Sep 6;11(9):2137. doi: 10.3390/nu11092137.