Heliyon (Oct 2022)

Melatonin suppresses the antiviral immune response to EMCV infection through intracellular ATP deprivation caused by mitochondrial fragmentation

  • Mariko Kikuchi,
  • Miki Kadena,
  • Haruka Fukamachi,
  • Takashi Takaki,
  • Shohei Matsui,
  • Sumire Hoashi-Takiguchi,
  • Hirobumi Morisaki,
  • Nataša Trtić,
  • Mina Mori,
  • Mie Kurosawa,
  • Momoe Itsumi,
  • Takahiro Funatsu,
  • Atsuo Sakurai,
  • Seikou Shintani,
  • Hiroki Kato,
  • Takashi Fujita,
  • Yasubumi Maruoka,
  • Hirotaka Kuwata

Journal volume & issue
Vol. 8, no. 10
p. e11149

Abstract

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Melatonin, a sleep hormone derived from the pineal gland, has an anti-inflammatory effect on the immune system in addition to modulating the brain nervous system. Previous studies have shown that melatonin suppresses signaling pathways downstream of multiple pattern recognition receptors on the innate immune cells during pathogen infection, but the specific mechanism of suppression has not been well understood. Using an encephalomyocarditis virus (EMCV) infection model in macrophages, we investigated the effects of melatonin on the antiviral response in innate immunity and found that melatonin attenuated the uptake of viral particles into macrophages. Furthermore, melatonin suppressed cytoskeletal regulation by decreasing ATP production by mitochondria. Finally, in an in vivo infection experiment, we also found that melatonin administration partially exacerbated the infection in the mouse brain. These results suggest that melatonin may have an inhibitory effect on excessive inflammation by suppressing cytoskeletal regulation in the innate immune system, but also suggest that suppression of inflammation may lead to insufficient protection against EMCV infection in vivo.

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