Monocytes maintain central nervous system homeostasis following helminth-induced inflammation

Jianya Peng, Chandler B. Sy, John J. Ponessa, Alexander D. Lemenze, Christina M. Hernandez, Juan M. Inclan-Rico, Arman Sawhney, Hannah G. Federman, Krupa Chavan, Vanessa Espinosa, Sergei V. Kotenko, Amariliz Rivera, Mark C. Siracusa

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroimmune interactions are crucial for regulating immunity and inflammation. Recent studies have revealed that the central nervous system (CNS) senses peripheral inflammation and responds by releasing molecules that limit immune cell activation, thereby promoting tolerance and tissue integrity. However, the extent to which this is a bidirectional process, and whether peripheral immune cells also promote tolerance mechanisms in the CNS remains poorly defined. Here we report that helminth-induced type 2 inflammation promotes monocyte responses in the brain that are required to inhibit excessive microglial activation and host death. Mechanistically, infection-induced monocytes express YM1 that is sufficient to inhibit tumor necrosis factor production from activated microglia. Importantly, neuroprotective monocytes persist in the brain, and infected mice are protected from subsequent lipopolysaccharide-induced neuroinflammation months after infection-induced inflammation has resolved. These studies demonstrate that infiltrating monocytes promote CNS homeostasis in response to inflammation in the periphery and demonstrate that a peripheral infection can alter the immunologic landscape of the host brain.

Original languageAmerican English
Article numbere2201645119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number37
DOIs
StatePublished - Sep 13 2022
Externally publishedYes

ASJC Scopus subject areas

  • General

Keywords

  • helminth
  • innate immune cells
  • monocyte
  • neuroimmune cross-talk

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