Author
Listed:
- Jin Kyung Kim
(Chungnam National University School of Medicine
Chungnam National University School of Medicine
Chungnam National University School of Medicine)
- Yi Sak Kim
(Chungnam National University School of Medicine
Chungnam National University School of Medicine
Chungnam National University School of Medicine)
- Hye-Mi Lee
(Chungnam National University School of Medicine
Chungnam National University School of Medicine)
- Hyo Sun Jin
(Chungnam National University Hospital)
- Chiranjivi Neupane
(Chungnam National University School of Medicine
Chungnam National University School of Medicine)
- Sup Kim
(Chungnam National University School of Medicine
Chungnam National University School of Medicine
Chungnam National University School of Medicine)
- Sang-Hee Lee
(Seoul National University)
- Jung-Joon Min
(Chonnam National University Medical School)
- Miwa Sasai
(Osaka University)
- Jae-Ho Jeong
(Chonnam National University Medical School
Chonnam National University Graduate School)
- Seong-Kyu Choe
(Wonkwang University School of Medicine)
- Jin-Man Kim
(Chungnam National University School of Medicine)
- Masahiro Yamamoto
(Osaka University)
- Hyon E. Choy
(Chonnam National University Medical School
Chonnam National University Graduate School)
- Jin Bong Park
(Chungnam National University School of Medicine
Chungnam National University School of Medicine)
- Eun-Kyeong Jo
(Chungnam National University School of Medicine
Chungnam National University School of Medicine
Chungnam National University School of Medicine)
Abstract
Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that GABAergic activation enhances antimicrobial responses against intracellular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera. Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABAAR), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Our study identified a previously unappreciated role for GABAergic signaling in linking antibacterial autophagy to enhance host innate defense against intracellular bacterial infection.
Suggested Citation
Jin Kyung Kim & Yi Sak Kim & Hye-Mi Lee & Hyo Sun Jin & Chiranjivi Neupane & Sup Kim & Sang-Hee Lee & Jung-Joon Min & Miwa Sasai & Jae-Ho Jeong & Seong-Kyu Choe & Jin-Man Kim & Masahiro Yamamoto & Hyo, 2018.
"GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections,"
Nature Communications, Nature, vol. 9(1), pages 1-17, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06487-5
DOI: 10.1038/s41467-018-06487-5
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Cited by:
- Luis Filipe Costa-Machado & Esther Garcia-Dominguez & Rebecca L. McIntyre & Jose Luis Lopez-Aceituno & Álvaro Ballesteros-Gonzalez & Andrea Tapia-Gonzalez & David Fabregat-Safont & Tobias Eisenberg & , 2023.
"Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models,"
Nature Communications, Nature, vol. 14(1), pages 1-22, December.
- Nelson V. Simwela & Luana Johnston & Paulina Pavinski Bitar & Eleni Jaecklein & Craig Altier & Christopher M. Sassetti & David G. Russell, 2024.
"Genome-wide screen of Mycobacterium tuberculosis-infected macrophages revealed GID/CTLH complex-mediated modulation of bacterial growth,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
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