title: Bone marrow-derived immune cells mediate sensitization to liver injury in a myeloid differentiation factor 88-dependent fashion.
abstract: Toll-like receptors (TLRs) expressed on both immune cells and hepatocytes recognize microbial danger signals and regulate immune responses. Previous studies showed that TLR9 and TLR2 mediate Propionibacterium acnes-induced sensitization to lipopolysaccharide-triggered acute liver injury in mice. Ligand-specific activation of TLR2 and TLR9 are dependent on the common TLR adaptor, myeloid differentiation factor 88 (MyD88). Here, we dissected the role of MyD88 in parenchymal and bone marrow (BM)-derived cells in liver sensitization. Using chimeric mice with green fluorescent protein-expressing BM cells, we identified that P. acnes-induced liver inflammatory foci are of BM origin. Chimeras with MyD88-deficient BM showed no inflammatory foci after P. acnes or TLR2+TLR9 challenge, suggesting that recruitment of inflammatory cells to the liver required MyD88 expression in BM-derived cells. Further, selective MyD88 deficiency in parenchymal cells in mice with wild-type BM failed to prevent inflammatory cell infiltration. These results demonstrate that MyD88 in immune cells rather than in liver parenchymal cells plays an important role in inflammatory cell recruitment and liver injury.
authors.affiliation: Department of Medicine, University of Massachusetts, Medical School, Worcester, MA 01605-2324, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Hritz
authors.forename: Arumugam
authors.initials: A
authors.lastname: Velayudham
authors.forename: Angela
authors.initials: A
authors.lastname: Dolganiuc
authors.forename: Karen
authors.initials: K
authors.lastname: Kodys
authors.forename: Pranoti
authors.initials: P
authors.lastname: Mandrekar
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kurt-Jones
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002678:Chimera; D005260:Female; D006099:Granuloma / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008107:Liver Diseases / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D011425:Propionibacterium acnes; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D049452:Green Fluorescent Proteins
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