title: Trichuris suis induces human non-classical patrolling monocytes via the mannose receptor and PKC: implications for multiple sclerosis.
abstract: BACKGROUND
  The inverse correlation between prevalence of auto-immune disorders like the chronic neuro-inflammatory disease multiple sclerosis (MS) and the occurrence of helminth (worm) infections, suggests that the helminth-trained immune system is protective against auto-immunity. As monocytes are regarded as crucial players in the pathogenesis of auto-immune diseases, we explored the hypothesis that these innate effector cells are prime targets for helminths to exert their immunomodulatory effects.
  
  
  RESULTS
  Here we show that soluble products of the porcine nematode Trichuris suis (TsSP) are potent in changing the phenotype and function of human monocytes by skewing classical monocytes into anti-inflammatory patrolling cells, which exhibit reduced trans-endothelial migration capacity in an in vitro model of the blood-brain barrier. Mechanistically, we identified the mannose receptor as the TsSP-interacting monocyte receptor and we revealed that specific downstream signalling occurs via protein kinase C (PKC), and in particular PKCδ.
  
  
  CONCLUSIONS
  This study provides comprehensive mechanistic insight into helminth-induced immunomodulation, which can be therapeutically exploited to combat various auto-immune disorders.
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. G.kooij@vumc.nl.
authors.forename: Gijs
authors.initials: G
authors.lastname: Kooij
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Rens
authors.initials: R
authors.lastname: Braster
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Koning
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Laan
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Tamara
authors.initials: T
authors.lastname: Los
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Anne Marieke
authors.initials: AM
authors.lastname: Eveleens
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: van der Pol
authors.affiliation: Divison of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Förster-Waldl
authors.affiliation: Divison of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Kaan
authors.initials: K
authors.lastname: Boztug
authors.affiliation: Hôpital Femme Mère Enfant, Hospices Civils de Lyon and Université de Lyon, Lyon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Belot
authors.affiliation: Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Katka
authors.initials: K
authors.lastname: Szilagyi
authors.affiliation: Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaap D
authors.initials: JD
authors.lastname: van Buul
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
authors.affiliation: Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000469:parasitology* / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D009000:Monocytes / Q000469:parasitology* / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014258:Trichuris / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011493:Protein Kinase C