title: TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects.
abstract: The spores of pathogenic bacteria are involved in host entry and the initial encounter with the host immune system. How bacterial spores interact with host immunity, however, remains poorly understood. Here, we show that the spores ofBacillus anthracis(BA), the etiologic agent of anthrax, possess an intrinsic ability to induce host immune responses. This immunostimulatory activity is attributable to high amounts of RNA present in the spore surface layer. RNA-sensing TLRs, TLR7, and TLR13 in mice and their human counterparts, are responsible for detecting and triggering the host cell response to BA spores, whereas TLR2 mediates the sensing of vegetative BA. BA spores, but not vegetative BA, induce type I IFN (IFN-I) production. Although TLR signaling in itself affords protection against BA, spore RNA-induced IFN-I signaling is disruptive to BA clearance. Our study suggests a role for bacterial spore-associated RNA in microbial pathogenesis and illustrates a little known aspect of interactions between the host and spore-forming bacteria.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Min-Kyung
authors.identifier: 0000-0003-1492-7539
authors.initials: MK
authors.lastname: Choo
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Macrogen Inc., Seoul 08511, Republic of Korea.
authors.forename: Changhoon
authors.identifier: 0000-0003-1087-0424
authors.initials: C
authors.lastname: Kim
authors.affiliation: Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Kei
authors.identifier: 0000-0002-6791-4531
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Xiao-Dong
authors.identifier: 0000-0002-4349-6996
authors.initials: XD
authors.lastname: Li
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Xin
authors.identifier: 0000-0003-0956-3654
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239.
authors.forename: Mary
authors.initials: M
authors.lastname: Stenzel-Poore
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université, UM2, 13288 Marseille, France.
authors.forename: Lena
authors.identifier: 0000-0003-4619-697X
authors.initials: L
authors.lastname: Alexopoulou
authors.affiliation: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
authors.forename: Sankar
authors.identifier: 0000-0002-3227-0588
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Institute of Innate Immunity, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Eicke
authors.identifier: 0000-0003-1488-5666
authors.initials: E
authors.lastname: Latz
authors.affiliation: Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Ian R
authors.identifier: 0000-0002-2674-3991
authors.initials: IR
authors.lastname: Rifkin
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Zhijian J
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Department of Veterinary Pathobiology and Bond Life Science Center, University of Missouri, Columbia, MO 65211.
authors.forename: George C
authors.identifier: 0000-0003-4766-160X
authors.initials: GC
authors.lastname: Stewart
authors.affiliation: Macrogen Inc., Seoul 08511, Republic of Korea.
authors.forename: Hyonyong
authors.initials: H
authors.lastname: Chong
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 jmpark@cbrc2.mgh.harvard.edu.
authors.forename: Jin Mo
authors.identifier: 0000-0002-3458-5583
authors.initials: JM
authors.lastname: Park
mesh_terms: D000818:Animals; D001408:Bacillus anthracis / Q000276:immunology; D005786:Gene Expression Regulation / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D051379:Mice; D012329:RNA, Bacterial / Q000276:immunology*; D013171:Spores, Bacterial / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D012329:RNA, Bacterial; D051193:Toll-Like Receptors