Adrenergic modulation ofEscherichia coliO157:H7 adherence to the colonic mucosa

Abstract

Enteric neurotransmitters can modulate the biodefensive functions of the intestinal mucosa, but their role in mucosal interactions with enteropathogens is not well defined. Here we tested the hypothesis that norepinephrine (NE) modulates interactions between enterohemorrhagic Escherichia coli O157:H7 (EHEC) and the colonic epithelium. Mucosal sheets from porcine distal colon were mounted in Ussing chambers. Drugs and an inoculum of either Shiga toxin-negative or -positive EHEC were added to the contraluminal and luminal bathing medium, respectively. After 90 min, adherent bacteria were quantified by an adherence assay and by immunohistochemical methods; short-circuit current (I(sc)) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in I(sc) and EHEC adherence. NE did not alter adherence of a rodent-adapted, noninfectious E. coli strain or two porcine-adapted non-O157 E. coli strains. The actions of NE on EHEC adherence but not I(sc) were prevented by the alpha-adrenergic antagonist yohimbine and the PKA activator Sp-8-bromoadenosine-3',5'-cyclic monophosphorothioate. Like NE, the PKA inhibitor Rp-8-bromoadenosine-3',5'-cyclic monophosphorothioate or indirectly acting sympathomimetic agents increased EHEC adherence. Nerve fibers immunoreactive for the NE-synthesizing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase appeared to innervate the colonic epithelium. EHEC-like immunoreactivity on the colonic surface had the appearance of bacterial microcolonies and increased after NE treatment by a phentolamine-sensitive mechanism. Through interactions with alpha(2)-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection.

Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa

“…We tested the hypothesis that acute E. coli O157:H7 exposure to the colonic mucosa, a major target for infection by this microorganism, activates local neural reflexes linked to sIgA secretion. Previous studies in our laboratory demonstrate that significant adherence of E. coli O157:H7 to the porcine colonic mucosa occurs within 90 min of luminal inoculation (Green et al, 2004). Interactions between E. coli O157:H7 and the colonic mucosa over this time interval did not elicit a significant change in luminally-directed sIgA output.…”

“…The localization of IgA + plasmacytes to the colonic lamina propria appears to be mediated by chemokine-receptor interactions involving the mucosa-associated epithelial chemokine CCL28 with its cognate receptor CCR10 (Brandtzaeg and Johansen, 2005). Although presumptive cholinergic and adrenergic nerve fibers have been localized previously in the intestinal lamina propria (Schafer et al, 1998;Green et al, 2004), their anatomical relationship to the cellular components of the mucosal IgA system has not hitherto been examined. These nerve fibers lie in close proximity to both antibody-secreting cells and SCimmunoreactive epithelial cells and it is not possible, at a morphological level, to distinguish their precise cellular target.…”

“…The porcine distal colon was chosen as an experimental model, despite some interspecies variations, as intestinal immunity in swine is similar in many respects to that in humans (Snoeck et al, 2006). Furthermore, mucosal explants from the porcine colon have been used to investigate the neuroregulation of active epithelial ion transport (Brown and O'Grady, 1997) and the adrenergic modulation of Escherichia coli O157:H7 adherence (Green et al, 2004). The main objectives of the present investigation were to establish the presence of presumptive cholinergic and adrenergic nerve fibers in immune effector sites of the porcine colon and characterize the effects of the cholinomimetic drug carbamylcholine (CCh) and NE on luminally-directed sIgA secretion from isolated sheets of the colonic mucosa.…”

Sympathetic modulation of immunity: Relevance to disease

“…In contrast, sympathectomized mice given an injection of gram-positive Staphylococcus aureus have increased bacterial burden, an effect mediated by reduced HPA activity, lower IL-4 production by peritoneal cells, and decreased influx of lymphocytes into the peritoneal cavity [302]. To this end, the SNS may differentially affect the influx of inflammatory cells into bacterially infected sites by regulating adherence of bacteria to the gastrointestinal epithelium [304], chemokine production [305], and/or expression of cellular adhesion molecules [306]. The SNS inhibits CC-chemokine ligand 3 or CCL3 production by subsets of neutrophils, which increased the susceptibility of thermally-injured mice to sepsis [305].…”

Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)

“…There are several methods for quantifying colonic injury 5,6,7 . One method, for example, uses a multi-parameter scale including: inflammation, extent involvement, regeneration, crypt damage, and percent involvement 8 .…”