Immune cells cross-talk to prevent damage-driving inflammation following CNS injury

Samuel David

Samuel David

New research by Samuel David at McGill University provides new insight on the role of macrophages and resident microglia following injury to the central nervous system. 

Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate at sites of central nervous system (CNS) injury. These cells have different origins – MDMs arise from the bone marrow throughout life, while microglia arise from the yolk sac during embryonic development and populate the CNS. Until very recently it was not possible to distinguish between these two cell types. It was also generally thought that they perform similar functions at sites of CNS injury such as spinal cord or brain injury or stroke. After CNS injury MDMs begin to infiltrate into the injury site. We asked why there is a need for MDMs to come into the CNS when microglia are already present, and whether the two cell types play different roles. In this paper we show that MDMs and microglia directly communicate with one another and differentially modulate each other’s functions via a prostaglandin mediated mechanism. Importantly, infiltrating MDMs (macrophages) suppress microglia-mediated phagocytosis and inflammation. This work provides the first evidence that macrophages entering the CNS from the circulation dampen microglial activation. Since microglia are the long-lived residents of the CNS, this may be a mechanism to prevent acute and chronic microglia-mediated inflammation, which may drive CNS damage in a variety of neurological disorders.

Original research article:

Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury.

Greenhalgh AD, Zarruk JG, Healy LM, Baskar Jesudasan SJ, Jhelum P, Salmon CK, Formanek A, Russo MV, Antel JP, McGavern DB, McColl BW, David S. PLoS Biol. 2018 Oct 17;16(10):e2005264.