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: Tatjana Eigenbrod, Karin Pelka, Eicke Latz, Bernd Kreikemeyer, Alexander H Dalpke
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 3 Pg. 1092-9 (Aug 01 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 26101323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• IL6 protein, human
• Interleukin-6
• RNA, Bacterial
• RNA, Ribosomal, 23S
• RNA, Small Interfering
• TLR8 protein, human
• TNF protein, human
• Tlr13 protein, mouse
• Toll-Like Receptor 8
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha
• Interferon-beta

Topics

• Animals
• Cell Line
• Humans
• Interferon-beta (metabolism)
• Interleukin-6 (metabolism)
• Macrophages (immunology)
• Methylation
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (immunology)
• RNA Interference
• RNA, Bacterial (genetics, immunology)
• RNA, Ribosomal, 23S (genetics, immunology)
• RNA, Small Interfering
• Streptococcus pyogenes (genetics, immunology)
• Toll-Like Receptor 8 (biosynthesis, genetics, immunology)
• Toll-Like Receptors (immunology, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)