GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections

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, Hyon E. Choy, Jin Bong Park () and Eun-Kyeong Jo ()
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Jin Kyung Kim: Chungnam National University School of Medicine
Yi Sak Kim: Chungnam National University School of Medicine
Hye-Mi Lee: Chungnam National University School of Medicine
Hyo Sun Jin: Chungnam National University Hospital
Chiranjivi Neupane: Chungnam National University School of Medicine
Sup Kim: 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
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
Jin Bong Park: Chungnam National University School of Medicine
Eun-Kyeong Jo: Chungnam National University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06487-5

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