Immunomodulatory activities of RNA species derived from commensal and pathogenic bacteria

Thesis Type: Postgraduate

Institution Of The Thesis: Orta Doğu Teknik Üniversitesi, Faculty of Arts and Sciences, Department of Biology, Turkey

Approval Date: 2017


Consultant: MAYDA GÜRSEL


Bacterial RNAs are recognized by various types of immune sensors. Here, we aimed to investigate the differential immune activation mediated by RNAs purified from commensal or pathogenic bacteria. For this, total RNAs and/or individual ribosomal RNAs (5S, 16S and 23S) were isolated from two commensal bacteria, Lactobacillus salivarious and Lactobacillus fermentum and two pathogens, Listeria monocytogenes, and Streptococcus pyogenes. Bacterial RNA species isolated from pathogens induced stronger pro-inflammatory cytokine production in human peripheral blood mononuclear cells (hPBMCs) and triggered activation of NF-κB/AP-1 in HEK-Blue cells expressing TLR3 or TLR7 receptors. Conversely, significant amount of type I IFN production was induced following delivery of commensal RNAs (total RNAs and 23S rRNAs), but not pathogenic RNAs, to cytosol. Moreover dsRNA content of commensal derived RNAs was shown to be higher than pathogen derived RNAs. These findings suggest the involvement of cytosolic dsRNA sensors like RIG-I and MDA-5 in commensal but not pathogen derived RNA recognition. Data further showed that the major type I IFN producing cells responding to commensal RNAs were monocytes but not plasmacytoid dendritic cells (pDCs). Interferogenic activity of commensal origin RNAs was also tested in human monocyte cell line THP-1, confirming the results obtained using primary monocytes. In conclusion, our data implicate that RNAs from commensals and pathogens are recognized differentially by the immune system to initiate either a type I interferon or a pro-inflammatory cytokine dominated immune response.