title: Chitin induces upregulation of B7-H1 on macrophages and inhibits T-cell proliferation.
abstract: Chitin is a highly abundant glycopolymer, which serves as structural component in fungi, arthropods and crustaceans but is not synthesized by vertebrates. However, vertebrates express chitinases and chitinase-like proteins, some of which are induced by infection with helminths suggesting that chitinous structures may be targets of the immune system. The chitin-induced modulations of the innate and adaptive immune responses are not well understood. Here, we demonstrate that intranasal administration of OVA and chitin resulted in diminished T-cell expansion and Th2 polarization as compared with OVA administration alone. Chitin did not promote nor attenuate Th2 polarization in vitro. Chitin-exposed macrophages inhibited proliferation of CD4(+) T cells in a cell-cell contact-dependent manner. Chitin induced upregulation of the inhibitory ligand B7-H1 (PD-L1) on macrophages independently of MyD88, TRIF, TLR2, TLR3, TLR4 and Stat6. Inhibition of T-cell proliferation was largely dependent on B7-H1, as the effect was not observed in cocultures with cells from B7-H1-deficient mice.
authors.affiliation: Institute for Immunology, Medical Faculty, University of Munich, Munich, Germany.
authors.forename: Claudia J
authors.initials: CJ
authors.lastname: Wagner
authors.forename: Silke
authors.initials: S
authors.lastname: Huber
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wirth
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002686:Chitin / Q000276:immunology / Q000494:pharmacology*; D018920:Coculture Techniques; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D010455:Peptides / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000276:immunology; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D051193:Toll-Like Receptors; D002686:Chitin; D010047:Ovalbumin