Translocated Legionella pneumophila small RNAs mimic eukaryotic microRNAs targeting the host immune response

Tobias Sahr (1, 2) , Pedro Escoll (1, 2) , Christophe Rusniok (1, 2) , Sheryl Bui (3) , Gérard Pehau-Arnaudet (4) , Gregory Lavieu (3) , Carmen Buchrieser (1, 2)

1 Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria
2 UPCité - Université Paris Cité
3 MSC - Matière et Systèmes Complexes
4 UTechS UBI - Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform

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.

Domains: Microbiology and Parasitology

Tobias Sahr, Pedro Escoll, Christophe Rusniok, Sheryl Bui, Gérard Pehau-Arnaudet, et al.. Translocated Legionella pneumophila small RNAs mimic eukaryotic microRNAs targeting the host immune response. Nature Communications, 2022, 13 (1), pp.762. ⟨10.1038/s41467-022-28454-x⟩. ⟨pasteur-03608322⟩