title: The impact of serine protease HtrA in apoptosis, intestinal immune responses and extra-intestinal histopathology during Campylobacter jejuni infection of infant mice.
abstract: BACKGROUND
  Campylobacter jejuni has emerged as a leading cause of bacterial enterocolitis. The serine protease HtrA has been shown to be a pivotal, novel C. jejuni virulence factor involved in cell invasion and transmigration across polarised epithelial cells in vitro. However, the functional relevance of the htrA gene for the interaction of C. jejuni with the host immune system in the infant mouse infection model has not been investigated so far.
  
  
  RESULTS
  Here we studied the role of C. jejuni htrA during infection of 3-weeks-old infant mice. Immediately after weaning, conventional wild-type mice were perorally infected with the NCTC11168∆htrA mutant (∆htrA) or the parental wild-type strain. Approximately one third of infected infant mice suffered from bloody diarrhea until day 7 post infection (p.i.), whereas colonic histopathological changes were rather moderate but comparable between the two strains. Interestingly, parental, but not ∆htrA mutant infected mice, displayed a multifold increase of apoptotic cells in the colonic mucosa at day 7 p.i., which was paralleled by higher colonic levels of pro-inflammatory cytokines such as TNF-α and IFN-γ and the matrix-degrading enzyme matrixmetalloproteinase-2 (MMP-2). Furthermore, higher numbers of proliferating cells could be observed in the colon of ∆htrA infected mice as compared to the parental wild-type strain. Remarkably, as early as 7 days p.i. infant mice also exhibited inflammatory changes in extra-intestinal compartments such as liver, kidneys and lungs, which were less distinct in kidneys and lungs following ∆htrA versus parental strain infection. However, live C. jejuni bacteria could not be found in these organs, suggesting the induction of systemic effects during intestinal infection.
  
  
  CONCLUSIONS
  Upon C. jejuni ∆htrA strain infection of infant mice, intestinal and extra-intestinal pro-inflammatory immune responses were ameliorated in the infant mouse model system. Future studies will shed further light onto the molecular mechanisms of host-pathogen interactions.
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Alutis
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Grundmann
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen, Nuremberg, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Boehm
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen, Nuremberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tegtmeyer
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany.
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology / Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen, Nuremberg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
keywords: Apoptosis; Cell invasion; Conventional infant mice; Extra-intestinal immune responses; Hepatic; Host-pathogen-interaction; Innate immunity; Pulmonal histopathology; Renal; Ulcerative enterocolitis