An intestinal organ culture system uncovers a role for the nervous system in microbe-immune crosstalk

• Nissan Yissachar ^[1] ; Yan Zhou ^[1] ; Lloyd Ung ^[2]
  1. [1] Harvard Medical School

     Harvard Medical School

     City of Boston, Estados Unidos

     
  2. [2] Harvard University

     Harvard University

     City of Cambridge, Estados Unidos

     
• Localización: Cell, ISSN 0092-8674, Vol. 168, Nº. 6, 2017, págs. 1135-1148
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Investigation of host-environment interactions in the gut would benefit from a culture system that maintained tissue architecture yet allowed tight experimental control. We devised a microfabricated organ culture system that viably preserves the normal multicellular composition of the mouse intestine, with luminal flow to control perturbations (e.g., microbes, drugs). It enables studying short-term responses of diverse gut components (immune, neuronal, etc.). We focused on the early response to bacteria that induce either Th17 or RORg+ T-regulatory (Treg) cells in vivo. Transcriptional responses partially reproduced in vivo signatures, but these microbes elicited diametrically opposite changes in expression of a neuronal-specific gene set, notably nociceptive neuropeptides. We demonstrated activation of sensory neurons by microbes, correlating with RORg+ Treg induction. Colonic RORg+ Treg frequencies increased in mice lacking TAC1 neuropeptide precursor and decreased in capsaicin-diet fed mice. Thus, differential engagement of the enteric nervous system may partake in bifurcating pro- or anti-inflammatory responses to microbes.