Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation

Karen De Vlaminck, Hannah Van Hove, Daliya Kancheva, Isabelle Scheyltjens, Ana Rita Pombo Antunes, Jonathan Bastos, Monica Vara-Perez, Leen Ali, Myrthe Mampay, Lauren Deneyer, Juliana Fabiani Miranda, Ruiyao Cai, Luc Bouwens, Dimitri De Bundel, Guy Caljon, Benoît Stijlemans, Ann Massie, Jo A Van Ginderachter, Roosmarijn E Vandenbroucke, Kiavash Movahedi

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)
53 Downloads (Pure)

Abstract

Microglia and border-associated macrophages (BAMs) are brain-resident self-renewing cells. Here, we examined the fate of microglia, BAMs, and recruited macrophages upon neuroinflammation and through resolution. Upon infection, Trypanosoma brucei parasites invaded the brain via its border regions, triggering brain barrier disruption and monocyte infiltration. Fate mapping combined with single-cell sequencing revealed microglia accumulation around the ventricles and expansion of epiplexus cells. Depletion experiments using genetic targeting revealed that resident macrophages promoted initial parasite defense and subsequently facilitated monocyte infiltration across brain barriers. These recruited monocyte-derived macrophages outnumbered resident macrophages and exhibited more transcriptional plasticity, adopting antimicrobial gene expression profiles. Recruited macrophages were rapidly removed upon disease resolution, leaving no engrafted monocyte-derived cells in the parenchyma, while resident macrophages progressively reverted toward a homeostatic state. Long-term transcriptional alterations were limited for microglia but more pronounced in BAMs. Thus, brain-resident and recruited macrophages exhibit diverging responses and dynamics during infection and resolution.

Original languageEnglish
Article numbere9
Pages (from-to)2085-2102
Number of pages18
JournalImmunity
Volume55
Issue number11
Early online date2022
DOIs
Publication statusPublished - 8 Nov 2022

Keywords

  • BAM
  • Trypanosoma
  • brain infection
  • infectious disease
  • inflammation
  • macrophage
  • microglia
  • monocyte
  • neuroimmunology
  • parasites

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