Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation

Tjakko J. van Ham*, Colleen A. Brady, Ruby D. Kalicharan, Nynke Oosterhof, Jeroen Kuipers, Anneke Veenstra-Algra, Klaas A. Sjollema, Randall T. Peterson, Harm H. Kampinga, Ben N. G. Giepmans

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

40 Citaten (Scopus)
233 Downloads (Pure)

Samenvatting

Many brain diseases involve activation of resident and peripheral immune cells to clear damaged and dying neurons. Which immune cells respond in what way to cues related to brain disease, however, remains poorly understood. To elucidate these in vivo immunological events in response to brain cell death we used genetically targeted cell ablation in zebrafish. Using intravital microscopy and large-scale electron microscopy, we defined the kinetics and nature of immune responses immediately following injury. Initially, clearance of dead cells occurs by mononuclear phagocytes, including resident microglia and macrophages of peripheral origin, whereas amoeboid microglia are exclusively involved at a later stage. Granulocytes, on the other hand, do not migrate towards the injury. Remarkably, following clearance, phagocyte numbers decrease, partly by phagocyte cell death and subsequent engulfment of phagocyte corpses by microglia. Here, we identify differential temporal involvement of microglia and peripheral macrophages in clearance of dead cells in the brain, revealing the chronological sequence of events in neuroinflammatory resolution. Remarkably, recruited phagocytes undergo cell death and are engulfed by microglia. Because adult zebrafish treated at the larval stage lack signs of pathology, it is likely that this mode of resolving immune responses in brain contributes to full tissue recovery. Therefore, these findings suggest that control of such immune cell behavior could benefit recovery from neuronal damage.

Originele taal-2English
Pagina's (van-tot)857-869
Aantal pagina's13
TijdschriftDisease models & mechanisms
Volume7
Nummer van het tijdschrift7
DOI's
StatusPublished - jul-2014

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