Page 58 - M. Immunology

[M. Immunology-35]

GABAergic activation enhances autophagy and phagosomal

maturation in macrophages during mycobacterial infection

Seul Gi Shin¹˙²˙³, Jin Kyung Kim¹˙²˙³, Yi Sak Kim¹˙²˙³, Hyun-Woo suh¹˙²˙³, Eun-Kyeong Jo¹˙²˙³˙*

¹Microbiology, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, ²Medical

Science, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, ³Infection Control
Convergence Research Center, Chungnam National University, Daejeon 35015, Republic of Korea

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter within the central nervous system and

has been extensively studied in neurological disorders, such as epilepsy, anxiety disorders, and schizophrenia.

However, the roles of GABA in antimicrobial host defenses are largely unknown. To define the mechanism by which
GABA triggers the antimicrobial host defense system during intracellular bacterial infection, we used RNA
sequencing to analyze the GABA-mediated, genome-wide transcriptional changes in bone marrow-derived

macrophages (BMDMs). GABA treatment led to an upregulation of numerous genes involved in autophagy in
BMDMs. When we next explored whether GABA activated autophagy, we found that GABA significantly increased

the mRNA expression levels of autophagy-related genes involved in autophagosome formation and autolysosome
maturation in BMDMs. We further showed that treatment of BMDMs with GABA or GABAAR agonists robustly

increased the autophagosomal membrane-associated LC3-II fractions and autophagic flux. In addition, we showed
that GABA-induced autophagy activation was required for phagosomal maturation during Mtb infection. Taken

together, both GABA and GABAergic activation enhanced activation of autophagy and phagosomal maturation
during Mtb infection.