title: TLR engagement prior to virus infection influences MHC-I antigen presentation in an epitope-dependent manner as a result of nitric oxide release.
abstract: Microorganisms contain PAMPs that can interact with different TLR-Ls. Cooperative signals from these receptors may modify innate and adaptive immune responses to invading pathogens. Therefore, a better understanding of the role TLRs play in initiating host defense during infections requires assessing the influence of multiple TLR engagement on pAPC activation and antigen presentation. In this study, we investigated the effects of combined TLR2, TLR3, or TLR4 engagement on DC activation and the presentation of LCMV antigens focusing on the major epitopes derived from NP and GP proteins encoded by the virus. Our results demonstrate that combined TLR ligation affected antigen presentation of NP(205-212), GP(33-41), and GP(276-286), but not NP(396-404). The altered antigen presentation was associated with changes in proteasomal activities and NO production as a result of TLR engagement. Taken together, the data demonstrate that combined TLR ligation could result in changes of innate effectors that may directly influence the adaptive immune response.
authors.affiliation: Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Attiya
authors.initials: A
authors.lastname: Alatery
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kus
authors.forename: Sameh
authors.initials: S
authors.lastname: Basta
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002918:Chymotrypsin / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015536:Down-Regulation; D000939:Epitopes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D008024:Ligands; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D018836:Inflammation Mediators; D008024:Ligands; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D002918:Chymotrypsin; D046988:Proteasome Endopeptidase Complex