Brain defence by the extracellular matrix protein Cochlin

The vertebrate brain is protected from infection by tight barriers. However, several barrier structures, including circumventricular organs and the choroid plexus, can potentially be breached by pathogens. Here, we show that Cochlin, a collagen-binding protein that is cleaved during infection to release the bacteria-aggregating and cytokine-inducing LCCL domain, contributes to defence at these regions. Transcriptome analysis and in situ hybridisation indicate that cochlin is expressed in the pineal gland, area postrema, choroid plexus and discrete regions of the meninges of zebrafish, mice and humans. Cochlin expression transiently increases in the brain of zebrafish larvae infected with Mycobacterium marinum and delivery of recombinant Cochlin reduces bacterial load.

Mutation of cochlin inhibits clearance of the bacteria from the brain, and this is reversed by supplying the LCCL domain. Barrier tissues thus contribute to vertebrate brain defence by secreting Cochlin, raising the possibility for therapeutic use of Cochlin in brain infection.