title: Transcriptomic and proteomic analyses reveal key innate immune signatures in the host response to the gastrointestinal pathogen Campylobacter concisus.
abstract: Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus, which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia n.kaakoush@unsw.edu.au.
authors.forename: Nadeem O
authors.initials: NO
authors.lastname: Kaakoush
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Nandan P
authors.initials: NP
authors.lastname: Deshpande
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Si Ming
authors.initials: SM
authors.lastname: Man
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Burgos-Portugal
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Faisal A
authors.initials: FA
authors.lastname: Khattak
authors.affiliation: Biological Mass Spectrometry Facility, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Raftery
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia Ramaciotti Centre for Gene Function Analysis, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Wilkins
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Mitchell
mesh_terms: D001483:Base Sequence; D002167:Campylobacter / Q000276:immunology*; D002169:Campylobacter Infections / Q000276:immunology*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000276:immunology* / Q000382:microbiology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D013058:Mass Spectrometry; D035683:MicroRNAs / Q000235:genetics; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D060066:Protein Interaction Maps; D040901:Proteomics; D062085:RNA, Long Noncoding / Q000235:genetics; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology*; D050791:STAT Transcription Factors / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D050835:Interferon Regulatory Factors; D035683:MicroRNAs; D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; D062085:RNA, Long Noncoding; D051192:Receptors, Pattern Recognition; D050791:STAT Transcription Factors; C115163:CREB1 protein, human; C525709:MIR221, human; C076700:IFI16 protein, human