Neuronal Interactions with Microbes in Pain and Host Defense

The sensory nervous system is constantly exposed to microbes at barrier tissues such as the skin and gut. We and other have found that nociceptors can directly sense bacteria and their products to mediate pain. During gram-positive infections, nociceptors can directly detect bacterial pore-forming toxins and signal to immune cells to modulate the outcome of infection. Therefore, the nervous system plays an active role in host defense. We recently found that both mouse and human nociceptors express ANTXR2 (CMG2), the high affinity receptor for anthrax toxins derived from Bacillus anthracis. Anthrax edema toxin (ET), consisting of protective antigen (PA) and edema factor (EF), specifically induced analgesic effects when administered intrathecally into mice. ET reduced baseline heat and mechanical nociception and had analgesic effects in inflammatory and neuropathic pain mouse models. ET led to transcriptional changes in DRG and blockade of transmission at central terminals of nociceptors. We could also engineer the anthrax toxins to deliver exogenous molecular cargoes into nociceptors via a PA+LFn based system to modulate pain signaling. Therefore, understanding microbial factors that act on sensory neurons could lead to novel approaches to treat pain and improve host defense. Isaac M. Chiu1 1. Harvard Medical School, Department of Immunology, Boston, MA, 02115