title: IL-23 prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage.
abstract: OBJECTIVE
  The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage.
  
  
  METHODS
  IL-23p19(-/-), IL-17A/F(-/-), CCR2(-/-), and wild-type (WT) mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. Liver-specific gene and protein expression during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19(-/-) and WT mice to investigate the role of IL-13 in disease outcome.
  
  
  RESULTS
  Liver damage in infected IL-23p19(-/-), IL-17A/F(-/-), and CCR2(-/-) mice was strongly attenuated compared with that in WT mice. IL-23p19(-/-) mice showed reduced accumulation of IL-17 and CCL2 mRNA and proteins. Increased numbers of IL-13-producing CD11b(+)Ly6C(lo) monocytes were associated with disease attenuation in IL-23p19(-/-) mice. Immuno-depletion of IL-13 in IL-23p19(-/-) mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery.
  
  
  CONCLUSIONS
  The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL-13 secreted by CD11b(+)Ly6C(lo) monocytes may be associated with recovery from liver damage. An IL-13/anti-IL13-mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Jill
authors.initials: J
authors.lastname: Noll
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Helk
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Fehling
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Bernin
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Marggraff
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
authors.affiliation: Department of Molecular Immunology and Gastroenterology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.affiliation: Department of Molecular Immunology and Gastroenterology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Penelope
authors.initials: P
authors.lastname: Pelczar
authors.affiliation: Department and Clinic for Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.affiliation: Department and Clinic for Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Ittrich
authors.affiliation: Department of Bioinformatics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Otto
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.affiliation: Division of Infection Immunology, Research Center Borstel, Borstel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.affiliation: Department of Medicine III, University Hospital Aachen, Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Bruchhaus
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Egbert
authors.initials: E
authors.lastname: Tannich
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. Electronic address: lotter@bnitm.de.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Lotter
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D004748:Entamoeba histolytica / Q000302:isolation & purification*; D004749:Entamoebiasis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics*; D053759:Interleukin-23 / Q000096:biosynthesis / Q000235:genetics*; D008109:Liver Diseases, Parasitic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction
chemical_list: D000950:Antigens, Ly; D018793:Interleukin-13; D053759:Interleukin-23; C494192:Ly-6C antigen, mouse; D004247:DNA
keywords: IL-13-dependent liver repair; IL-23/IL-17 immunopathology; Parasite-induced liver damage; Regenerative Ly6C(lo) monocytes