title: Proteome and Secretome Analysis Reveals Differential Post-transcriptional Regulation of Toll-like Receptor Responses.
abstract: The innate immune system is the organism's first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level.
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Marijke
authors.initials: M
authors.lastname: Koppenol-Raab
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Virginie
authors.initials: V
authors.lastname: Sjoelund
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Manes
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Gottschalk
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Dutta
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Benet
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
authors.forename: Iain D C
authors.initials: ID
authors.lastname: Fraser
authors.affiliation: From the ‡Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892 nitalazarau@niaid.nih.gov.
authors.forename: Aleksandra
authors.identifier: 0000-0002-8523-605X
authors.initials: A
authors.lastname: Nita-Lazar
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D020543:Proteome / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D000067996:RAW 264.7 Cells; D012323:RNA Processing, Post-Transcriptional; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D020543:Proteome; D051193:Toll-Like Receptors