title: Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut.
abstract: Vagal activation can reduce inflammation and disease activity in various animal models of intestinal inflammation via the cholinergic anti-inflammatory pathway. In the current model of this pathway, activation of descending vagal efferents is dependent on a signal initiated by stimulation of vagal afferents. However, little is known about how vagal afferents are activated, especially in the context of subclinical or clinical pathogenic bacterial infection. To address this question, we first determined if selective lesions of capsaicin-sensitive vagal afferents altered c-Fos expression in the nucleus of the solitary tract (nTS) after mice were inoculated with either Campylobacter jejuni or Salmonella typhimurium. Our results demonstrate that the activation of nTS neurons by intraluminal pathogenic bacteria is dependent on intact, capsaicin sensitive vagal afferents. We next determined if inflammatory mediators could cause the observed increase in c-Fos expression in the nTS by a direct action on vagal afferents. This was tested by the use of single-cell calcium measurements in cultured vagal afferent neurons. We found that tumor necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) directly activate cultured vagal afferent neurons and that almost all TNFα and LPS responsive neurons were sensitive to capsaicin. We conclude that activation of the afferent arm of the parasympathetic neuroimmune reflex by pathogenic bacteria in the gut is dependent on capsaicin sensitive vagal afferent neurons and that the release of inflammatory mediators into intestinal tissue can be directly sensed by these neurons.
authors.affiliation: Programs in Neuroscience, Washington State University, Pullman, WA 99164, USA. triley@vetmed.wsu.edu
authors.forename: T P
authors.initials: TP
authors.lastname: Riley
authors.forename: J M
authors.initials: JM
authors.lastname: Neal-McKinney
authors.forename: D R
authors.initials: DR
authors.lastname: Buelow
authors.forename: M E
authors.initials: ME
authors.lastname: Konkel
authors.forename: S M
authors.initials: SM
authors.lastname: Simasko
mesh_terms: D000818:Animals; D002169:Campylobacter Infections / Q000382:microbiology / Q000473:pathology; D002211:Capsaicin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009475:Neurons, Afferent / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012480:Salmonella Infections / Q000382:microbiology / Q000473:pathology; D014630:Vagus Nerve / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology
chemical_list: D002211:Capsaicin