Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells

Kousuke Yonemoto; Fumihiko Fujii; Ryoji Taira; Masahiro Ohgidani; Katsuhide Eguchi; Sayaka Okuzono; Yuko Ichimiya; Yuri Sonoda; Pin Fee Chong; Hironori Goto; Hikaru Kanemasa; Yoshitomo Motomura; Masataka Ishimura; Yuhki Koga; Keita Tsujimura; Takao Hashiguchi; Hiroyuki Torisu; Ryutaro Kira; Takahiro A Kato; Yasunari Sakai; Shouichi Ohga

doi:10.1016/j.clim.2023.109756

Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells

Clin Immunol. 2023 Oct:255:109756. doi: 10.1016/j.clim.2023.109756. Epub 2023 Sep 9.

Authors

Kousuke Yonemoto¹, Fumihiko Fujii¹, Ryoji Taira¹, Masahiro Ohgidani², Katsuhide Eguchi¹, Sayaka Okuzono³, Yuko Ichimiya¹, Yuri Sonoda¹, Pin Fee Chong¹, Hironori Goto¹, Hikaru Kanemasa¹, Yoshitomo Motomura¹, Masataka Ishimura¹, Yuhki Koga¹, Keita Tsujimura⁴, Takao Hashiguchi⁵, Hiroyuki Torisu⁶, Ryutaro Kira⁷, Takahiro A Kato⁸, Yasunari Sakai⁹, Shouichi Ohga¹

Affiliations

¹ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Functional Anatomy and Neuroscience, Asahikawa Medical University, Hokkaido, Japan.
³ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Section of Pediatrics, Department of Medicine, Fukuoka Dental College, Fukuoka, Japan.
⁴ Group of Brain Function and Development, Neuroscience Institute of the Graduate School of Science, Nagoya University, Aichi, Japan; Research Unit for Developmental Disorders, Institute for Advanced Research, Nagoya University, Aichi, Japan.
⁵ Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
⁶ Section of Pediatrics, Department of Medicine, Fukuoka Dental College, Fukuoka, Japan.
⁷ Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
⁸ Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁹ Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].

PMID: 37678717
DOI: 10.1016/j.clim.2023.109756

Abstract

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14^high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

Keywords: Divergence; Heterogeneity; Immunoreactivity; Microglia; Mitochondria; and CD14.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Flow Cytometry
Gene Expression
Humans
Lipopolysaccharides / pharmacology
Microglia* / metabolism
Neuroinflammatory Diseases*

Substances

Lipopolysaccharides