Kaakoush Nadeem O, Deshpande Nandan P, Man Si Ming, Burgos-Portugal Jose A, Khattak Faisal A, Raftery Mark J, Wilkins Marc R, Mitchell Hazel M
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.
Infect Immun. 2015 Feb;83(2):832-45. doi: 10.1128/IAI.03012-14. Epub 2014 Dec 8.
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.
弯曲杆菌属内的致病物种给全球健康带来了相当大的负担。简明弯曲杆菌是一种新兴病原体，在急性和慢性胃肠疾病中起作用。尽管对弯曲杆菌的毒力机制进行了持续研究，但对于宿主对弯曲杆菌感染的免疫反应特征知之甚少。在本研究中，我们描述了在感染了具有黏附和侵袭性的简明弯曲杆菌菌株的分化THP-1巨噬细胞中，对简明弯曲杆菌感染的先天性免疫反应的全面全球概况。使用RNA测序（RNA-seq）、定量PCR（qPCR）、质谱分析和共聚焦显微镜，我们观察到模式识别受体的差异表达以及DNA和RNA传感分子的强烈上调。特别是，我们在感染简明弯曲杆菌的巨噬细胞中观察到IFI16炎性小体组装。转录组的全球概况显示，感染简明弯曲杆菌后共有8343个转录本受到显著调控，其中包括涉及CREB1、NF-κB、STAT和干扰素调节因子信号传导的关键炎症途径的激活。感染后有13种微小RNA和333种非编码RNA受到显著调控，其中包括与结直肠癌发生相关的MIR221。这项研究代表了我们在理解宿主对简明弯曲杆菌感染的识别和先天性免疫反应方面的重大进展。
