Abstract
Legionella pneumophila is an intracellular bacterial pathogen that can cause a severe form of pneumonia in humans, a phenotype evolved through interactions with aquatic protozoa in the environment. Here, we show that L. pneumophila uses extracellular vesicles to translocate bacterial small RNAs (sRNAs) into host cells that act on host defence signalling pathways. The bacterial sRNA RsmY binds to the UTR of ddx58 (RIG-I encoding gene) and cRel, while tRNA-Phe binds ddx58 and irak1 collectively reducing expression of RIG-I, IRAK1 and cRel, with subsequent downregulation of IFN-β. Thus, RsmY and tRNA-Phe are bacterial trans-kingdom regulatory RNAs downregulating selected sensor and regulator proteins of the host cell innate immune response. This miRNA-like regulation of the expression of key sensors and regulators of immunity is a feature of L. pneumophila host-pathogen communication and likely represents a general mechanism employed by bacteria that interact with eukaryotic hosts.
Highlights
Legionella pneumophila is an intracellular bacterial pathogen that can cause a severe form of pneumonia in humans, a phenotype evolved through interactions with aquatic protozoa in the environment
Our results indicate that the absence of RsmY in Lp-extracellular vesicles (EVs) resulted in an up-regulation of IFN-ß in the supernatant, whereas the transfection of RsmY-RNA lead to a reduced IFN-ß secretion compared to the control RNA, in agreement with our model that RsmY contained within the LpEVs is biological active in the host cell and plays a role in dampening the immune response of host cells to infection
We found that L. pneumophila-derived EVs (Lp-EVs) show a unique RNA profile, different from the RNA content of the bacterial cells from which they derived, as 39 small RNAs (sRNAs) are highly enriched in the Lp-EVs suggesting that RNA is not randomly incorporated
Summary
Legionella pneumophila is an intracellular bacterial pathogen that can cause a severe form of pneumonia in humans, a phenotype evolved through interactions with aquatic protozoa in the environment. RsmY and tRNA-Phe are bacterial transkingdom regulatory RNAs downregulating selected sensor and regulator proteins of the host cell innate immune response This miRNA-like regulation of the expression of key sensors and regulators of immunity is a feature of L. pneumophila host-pathogen communication and likely represents a general mechanism employed by bacteria that interact with eukaryotic hosts. Evolutionary analyses strongly suggested that they had been acquired by horizontal gene transfer from their protozoan hosts during co-evolution[9,10,11,12,13] The translocation of these different bacterial proteins in the host cell is a vital part of a successful infection. It is not known whether Lp-EVs contain RNAs
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