Microbes' roadmap to neurons

Key Points Infections by microbes cause major diseases in the nervous system but are relatively neglected in the neuroscience community. Mechanisms have evolved by which microbes can bypass the barriers that protect the nervous system and target neuronal populations in various regions of the brain. Immune responses in the nervous system are generally not robust. This allows microbes to hide and survive in this relatively protective environment, but can also lead to rapid, life-threatening infections. Knowledge on the fundamental cellular mechanisms used by microbes to propagate to the nervous system is important for developing host-directed drugs as adjunctive treatments with antimicrobial drugs. Infections with microbes can have late-onset effects on nervous system functions, leading to behaviour changes and epilepsy. Research on the pathogenic events during these long latency periods could aid the development of strategies to prevent the appearance of these signs of disease. Studies on the interactions between neurons and microbes also provide powerful tools to decipher basic neuronal functions and molecular sorting mechanisms. Despite protective barriers, the nervous system is vulnerable to the invasion of pathogens. This Review discusses mechanisms by which microbes enter the nervous system and cause persistent or life-threatening infections. The nervous system is protected by barriers that restrict the invasion of pathogens. Nevertheless, mechanisms have evolved by which microbes can pass these barriers, enter and exit neurons and target various regions of the nervous system. In the brain, immune responses to pathogens are generally not robust, so microbes can hide and survive or, conversely, cause severe uncontrolled infections. Depending on their sites of entry and the regions that they target, microbes can cause diverse nervous system dysfunctions and even influence host behaviour to their own advantage. This Review discusses routes by which microbes can reach the nervous system and cause persistent or life-threatening infections.