The response of the innate immune system in the brain differs from the response in other organs

10 January 2015

BPRC - 1. The response of the innate immune system in the brain differs from the response in other organs

Macrophages are the cleaning cells of the body and are an important component of the innate immune system. Literally translated, the term macrophage means ‘wolverine’. Macrophages have useful functions within the body, removing among other things the remains of dead or damaged cells. They are also involved in the detection of pathogens and in controlling other immune cells. Many organs are populated by specific types of macrophages. Some of those are even derived from different progenitors. BPRC researchers have studied the properties of a macrophage type that is located in the brain, the so-called microglia. In particular, the response of these cells to inflammatory reactions was studied.

All macrophages can recognize pathogens and cellular damage through receptors, a type of antennas that allow them to scan the environment. When these antennae capture a signal, signaling molecules can be produced and secreted. One of these signaling molecules is IL-1β, a substance that plays an important role in the generation of fever and the control of other immune cells. IL-1β is produced only when the antennas of a specific receptor complex (the inflammasome) have captured a signal. The role of the inflammasome in microglia is still largely unexplored, in contrast to its role in other types of macrophages that extensively has been studied.

To investigate the role of the inflammosome in microglia, BPRC researchers have studied brain tissue from rhesus monkeys that were euthanized for other reasons. They determined the protein composition of microglia and performed an in-depth characterization of the activation and regulation of the inflammasome in microglia. This turned out to differ from other types of macrophages in several important aspects. The production of IL-1β in microglia was slower, but continued for prolonged times compared to other macrophages. Moreover, the production of IL-1β in microglia was not entirely dependent on the so-called inflammasome. This is in contrast to other macrophages, in which the IL-1β production was completely dependent on the inflammasome. Therefore, other (as yet unknown) mechanisms play a role in the production of IL-1β by microglia.

This is valuable information for the development of therapies that affect immune responses in the brains, for example in multiple sclerosis (MS). The results of this study have been published in the prestigious journal The Journal of Neuroscience.