title: TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes.
abstract: Microbial nucleic acids constitute an important group of pathogen-associated molecular patterns (PAMPs) that efficiently trigger innate immune activation. In mice, TLR13 has recently been identified to sense a highly conserved region within bacterial 23S rRNA. However, TLR13 is not expressed in humans, and the identity of its human homolog remains elusive. Moreover, the contribution of bacterial RNA to the induction of innate immune responses against entire bacteria is still insufficiently defined. In the current study, we show that human monocytes respond to bacterial RNA with secretion of IL-6, TNF, and IFN-β, which is critically dependent on lysosomal maturation. Using small interfering RNA and overexpression, we unambiguously identify TLR8 as receptor for bacterial RNA in primary human monocyte-derived macrophages. We further demonstrate that the sequence motif sensed by TLR8 is clearly distinct from that recognized by TLR13. Moreover, TLR8-dependent detection of bacterial RNA was critical for triggering monocyte activation in response to infection with Streptococcus pyogenes. Bacterial RNA within streptococci was also a dominant stimulus for murine immune cells, highlighting the physiological relevance of RNA sensing in defense of infections.
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120 Heidelberg, Germany; tatjana.eigenbrod@med.uni-heidelberg.de.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Eigenbrod
authors.affiliation: Institute of Innate Immunity, University Hospital, University of Bonn, 53127 Bonn, Germany; and.
authors.forename: Karin
authors.initials: K
authors.lastname: Pelka
authors.affiliation: Institute of Innate Immunity, University Hospital, University of Bonn, 53127 Bonn, Germany; and.
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.affiliation: Institute of Medical Microbiology, Virology, and Hygiene, University of Rostock, 18057 Rostock, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120 Heidelberg, Germany;
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Dalpke
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D034622:RNA Interference; D012329:RNA, Bacterial / Q000235:genetics / Q000276:immunology*; D012338:RNA, Ribosomal, 23S / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D034741:RNA, Small Interfering; C495349:TLR8 protein, human; C439524:TNF protein, human; C539093:Tlr13 protein, mouse; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta