| First Author | Pinho-Ribeiro FA | Year | 2018 |
| Journal | Cell | Volume | 173 |
| Issue | 5 | Pages | 1083-1097.e22 |
| PubMed ID | 29754819 | Mgi Jnum | J:265326 |
| Mgi Id | MGI:6160622 | Doi | 10.1016/j.cell.2018.04.006 |
| Citation | Pinho-Ribeiro FA, et al. (2018) Blocking Neuronal Signaling to Immune Cells Treats Streptococcal Invasive Infection. Cell 173(5):1083-1097.e22 |
| abstractText | 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. |
