title: Acute infection with the intestinal parasite Trichuris muris has long-term consequences on mucosal mast cell homeostasis and epithelial integrity.
abstract: A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria. Furthermore, we also detected increased local and systemic levels of the mucosal mast cell protease MCPt-1, which correlated highly with the persistent epithelial mast cell population. Finally, the mast cells appeared to have striking consequences on epithelial barrier integrity, by regulation of gut permeability long after worm expulsion. These findings highlight the importance of mast cells not only in the early phases of infection but also at later stages, which has functional implications on the mucosal tissue.
authors.affiliation: Immunology Section, Department of Experimental Medical Sciences, Medical Faculty, Lund University, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sorobetea
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jacob Bak
authors.initials: JB
authors.lastname: Holm
authors.affiliation: Immunology Section, Department of Experimental Medical Sciences, Medical Faculty, Lund University, Lund, Sweden.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Henningsson
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Immunology Section, Department of Experimental Medical Sciences, Medical Faculty, Lund University, Lund, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Svensson-Frej
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D053818:Chymases / Q000378:metabolism; D004847:Epithelial Cells / Q000469:parasitology / Q000502:physiology*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics; D006706:Homeostasis; D006790:Host-Parasite Interactions; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D053818:Chymases; C509230:Mcpt1 protein, mouse
keywords: Acute parasite infection; Large-intestinal epithelium; MCPt-1; Mucosal mast cell; Trichuris muris