title: Campylobacter jejuniinfection of conventionally colonized mice lacking nucleotide-oligomerization-domain-2.
abstract: BACKGROUND
  The nucleotide-binding oligomerisaton protein 2 (NOD2) constitutes a pivotal sensor of bacterial muramyl dipeptide and assures expression of distinct antimicrobial peptides and mediators produced by enterocytes and immune cells directed against pathogens includingCampylobacter jejuni. We here elucidated the role of NOD2 during murineC. jejuniinfection in more detail.
  
  
  RESULTS
  Conventionally colonized NOD2 deficient (NOD2-/-) mice and corresponding wildtype (WT) counterparts were perorally infected withC. jejunistrain 81-176 on three consecutive days. The pathogen colonized both WT and NOD2-/-mice only sporadically until day 14 post infection (p.i.). However, the slightly higher prevalence ofC. jejuniin NOD2-/-mice was accompanied by higher intestinalEscherichia coliloads known to facilitateC. jejunicolonization. Neither overt macroscopic (clinical) nor microscopic sequelae (such as colonic epithelial apoptosis) could be observed upon murineC. jejuniinfection of either genotype. Innate immune responses were less distinctly induced inC. jejuniinfected NOD2-/-versus WT mice as indicated by lower colonic numbers of neutrophils in the former. Conversely, adaptive immune cell counts including T lymphocytes were higher in large intestines of NOD2-/-as compared to WT mice that were paralleled by increased colonic IL-6 secretion and higher TNF and IL-18 mRNA expression levels in large intestines of the former. Only in NOD2-/-mice, however, colonic IL-22 mRNA expression was down-regulated at day 14 p.i. Whereas viable commensal intestinal bacteria could exclusively be detected in mesenteric lymph nodes and livers of NOD2-/-mice, bacterial translocation rates to kidneys and spleen were NOD2 independent. Notably, large intestinal mRNA expression levels of mucin-2, constituting a pivotal factor involved in epithelial barrier integrity, were comparable in naive andC. jejuniinfected mice of either genotype.
  
  
  CONCLUSIONS
  NOD2 is involved in the well-balanced regulation of innate and adaptive pro-inflammatory immune responses of conventional mice uponC. jejuniinfection.
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Grundmann
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Alutis
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité-University Medicine Berlin, CC5, Campus Benjamin Franklin, FEM, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
keywords: Bacterial translocation; Campylobacter jejuni; Colonization resistance; IL-23/IL-22/IL-18 axis; In vivo infection; Intestinal microbiota; Nucleotide-oligomerization-domain-2 (NOD2); Pro-inflammatory immune responses