Citation:
Felipe A Pinho-Ribeiro, Buket Baddal, Rianne Haarsma, Maghnus O'Seaghdha, Nicole J Yang, Kimbria J Blake, Makayla Portley, Waldiceu A Verri, James B Dale, Michael R Wessels, and Isaac M Chiu. 2018. “Blocking Neuronal Signaling to Immune Cells Treats Streptococcal Invasive Infection.” Cell, 173, 5, Pp. 1083-1097.e22. Copy at http://www.tinyurl.com/y24flfuh
 | 9.44 MB |
Abstract:
The nervous system, the immune system, and microbial pathogens interact closely at barrier tissues. Here, we find that a bacterial pathogen, Streptococcus pyogenes, hijacks pain and neuronal regulation of the immune response to promote bacterial survival. Necrotizing fasciitis is a life-threatening soft tissue infection in which "pain is out of proportion" to early physical manifestations. We find that S. pyogenes, the leading cause of necrotizing fasciitis, secretes streptolysin S (SLS) to directly activate nociceptor neurons and produce pain during infection. Nociceptors, in turn, release the neuropeptide calcitonin gene-related peptide (CGRP) into infected tissues, which inhibits the recruitment of neutrophils and opsonophagocytic killing of S. pyogenes. Botulinum neurotoxin A and CGRP antagonism block neuron-mediated suppression of host defense, thereby preventing and treating S. pyogenes necrotizing infection. We conclude that targeting the peripheral nervous system and blocking neuro-immune communication is a promising strategy to treat highly invasive bacterial infections. VIDEO ABSTRACT.Notes:
- Chosen for cover article for Cell (May 17, 2018 issue).
- Preview by Kevin J Tracey. Neurons are the inflammatory problem. Cell May 17;173(5):1066-1068.
- Comment by M. Teresa Villanueva. Infectious diseases: The painful path to avoiding the immune system. Nature Reviews Drug Discov. 2018 Jul; 17(7):469.
- Featured by Harvard Medical School News, CBC radio broadcast, and Seeker Youtube video on Flesh-eating bacteria.
See also: Primary Research Papers