Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni

Brain Behav Immun. 2005 Jul;19(4):334-44. doi: 10.1016/j.bbi.2004.09.002.


Abundant evidence now supports the idea that multiple pathways or mechanisms underlie communication from the immune system to the brain. The presence of a variety of mechanisms suggests that they may each contribute something different to immunosensory signaling. For instance, brain mediated immune signal transduction is dependent upon the presence of circulating mediators whereas peripheral sensory nerves are more likely to be important early on in an infection, prior to elevation of circulating cytokines, or in local infections within the terminal fields of these nerves. To test the hypothesis that local infection in the gut activates vagal sensory neurons, we assessed expression of the neuronal activation marker c-Fos in neurons in the vagal sensory ganglia and in the primary sensory relay nucleus for the vagus, the nucleus of the solitary tract (nTS) in mice treated orally either with saline or live Campylobacter jejuni (C. jejuni). Male CF1 mice were inoculated orally with either C. jejuni or saline, and c-Fos expression in the vagal sensory neurons and brain 4-12 h later was assessed via immunohistochemistry. Oral inoculation with C. jejuni led to a significant increase in c-Fos expression in neurons bilaterally in the vagal ganglia, in the absence of elevated levels of circulating pro-inflammatory cytokines. C. jejuni treatment activated neurons in the nTS, as well as in brain regions associated with primary viscerosensory pathways and the central autonomic network. These findings provide evidence that peripheral sensory neurons contribute an early signal to the brain regarding potential pathogens.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism
  • Campylobacter Infections / blood
  • Campylobacter Infections / immunology*
  • Campylobacter jejuni / immunology*
  • Cecum / immunology*
  • Cecum / innervation
  • Cecum / microbiology
  • Cytokines / blood
  • Enteric Nervous System / physiology
  • Ganglia, Autonomic / physiology
  • Male
  • Mice
  • Neuroimmunomodulation / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Vagus Nerve / physiology*
  • Visceral Afferents / physiology*


  • Cytokines
  • Proto-Oncogene Proteins c-fos