False friends: Phagocytes as Trojan horses in microbial brain infections

Humans are constantly exposed to pathogenic microbes. The first line of cellular host defense is composed of “professional” phagocytes, cells that efficiently recognize pathogens, internalize them, and then marshal an array of antimicrobial mechanisms to destroy them. Nevertheless, successful pathogens evade or survive such attack. A particularly subversive strategy is to manipulate normal phagocyte behaviors to benefit the microbe, sometimes even turning the phagocyte from a threat to a safe haven. In this environment, the microbes can multiply while protected from immune surveillance, and in some cases, even travel to the most protected host site, the brain. This gives rise to the Trojan horse analogy: like the wooden horse that carried hidden enemies through the gates into the walled city of Troy, phagocytes carry intracellular microbes through the blood–brain barrier (BBB) into the central nervous system (CNS).