TLR13 Recognizes Bacterial 23S rRNA Devoid of Erythromycin Resistance-Forming Modification

被引:311
作者
Oldenburg, Marina [1 ]
Krueger, Anne [1 ]
Ferstl, Ruth [2 ]
Kaufmann, Andreas [3 ]
Nees, Gernot [3 ]
Sigmund, Anna [1 ]
Bathke, Barbara [4 ]
Lauterbach, Henning [4 ]
Suter, Mark [4 ,5 ]
Dreher, Stefan [2 ]
Koedel, Uwe [6 ]
Akira, Shizuo [7 ]
Kawai, Taro [7 ]
Buer, Jan [1 ]
Wagner, Hermann [2 ]
Bauer, Stefan [3 ]
Hochrein, Hubertus
Kirschning, Carsten J. [1 ]
机构
[1] Univ Duisburg Essen, Inst Med Microbiol, D-45147 Essen, Germany
[2] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany
[3] Univ Marburg, Inst Immunol, D-35043 Marburg, Germany
[4] Bavarian Nord GmbH, Dept Res Immunol, D-82152 Martinsried, Germany
[5] Univ Zurich, Inst Virol, CH-8006 Zurich, Switzerland
[6] Clin Univ Munich, Dept Neurol, D-81377 Munich, Germany
[7] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Osaka 5650871, Japan
关键词
TOLL-LIKE RECEPTORS; MACROLIDE RESISTANCE; DENDRITIC CELLS; LIPOPROTEINS; INFECTION; MUTATION; IMMUNITY; COMPLEX; SENSOR;
D O I
10.1126/science.1220363
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Host protection from infection relies on the recognition of pathogens by innate pattern-recognition receptors such as Toll-like receptors (TLRs). Here, we show that the orphan receptor TLR13 in mice recognizes a conserved 23S ribosomal RNA (rRNA) sequence that is the binding site of macrolide, lincosamide, and streptogramin group (MLS) antibiotics (including erythromycin) in bacteria. Notably, 23S rRNA from clinical isolates of erythromycin-resistant Staphylococcus aureus and synthetic oligoribonucleotides carrying methylated adenosine or a guanosine mimicking a MLS resistance-causing modification failed to stimulate TLR13. Thus, our results reveal both a natural TLR13 ligand and specific mechanisms of antibiotic resistance as potent bacterial immune evasion strategy, avoiding recognition via TLR13.
引用
收藏
页码:1111 / 1115
页数:5
相关论文
共 25 条
[1]   Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors [J].
Brightbill, HD ;
Libraty, DH ;
Krutzik, SR ;
Yang, RB ;
Belisle, JT ;
Bleharski, JR ;
Maitland, M ;
Norgard, MV ;
Plevy, SE ;
Smale, ST ;
Brennan, PJ ;
Bloom, BR ;
Godowski, PJ ;
Modlin, RL .
SCIENCE, 1999, 285 (5428) :732-736
[2]   The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling [J].
Brinkmann, Melanie M. ;
Spooner, Eric ;
Hoebe, Kasper ;
Beutler, Bruce ;
Ploegh, Hidde L. ;
Kim, You-Me .
JOURNAL OF CELL BIOLOGY, 2007, 177 (02) :265-275
[3]   Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex [J].
Buriánková, K ;
Doucet-Populaire, F ;
Dorson, O ;
Gondran, A ;
Ghnassia, JC ;
Weiser, J ;
Pernodet, JL .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (01) :143-150
[4]   TLR7: A new sensor of viral infection [J].
Crozat, K ;
Beutler, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (18) :6835-6836
[5]   Antibiotic resistance is ancient [J].
D'Costa, Vanessa M. ;
King, Christine E. ;
Kalan, Lindsay ;
Morar, Mariya ;
Sung, Wilson W. L. ;
Schwarz, Carsten ;
Froese, Duane ;
Zazula, Grant ;
Calmels, Fabrice ;
Debruyne, Regis ;
Golding, G. Brian ;
Poinar, Hendrik N. ;
Wright, Gerard D. .
NATURE, 2011, 477 (7365) :457-461
[6]   Macrophages recognize streptococci through bacterial single-stranded RNA [J].
Deshmukh, Sachin D. ;
Kremer, Bernhard ;
Freudenberg, Marina ;
Bauer, Stefan ;
Golenbock, Douglas T. ;
Henneke, Philipp .
EMBO REPORTS, 2011, 12 (01) :71-76
[7]   Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection [J].
Girardin, SE ;
Boneca, IG ;
Viala, J ;
Chamaillard, M ;
Labigne, A ;
Thomas, G ;
Philpott, DJ ;
Sansonetti, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (11) :8869-8872
[8]   A Toll-like receptor recognizes bacterial DNA [J].
Hemmi, H ;
Takeuchi, O ;
Kawai, T ;
Kaisho, T ;
Sato, S ;
Sanjo, H ;
Matsumoto, M ;
Hoshino, K ;
Wagner, H ;
Takeda, K ;
Akira, S .
NATURE, 2000, 408 (6813) :740-745
[9]   Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7 [J].
Hornung, V ;
Guenthner-Biller, M ;
Bourquin, C ;
Ablasser, A ;
Schlee, M ;
Uematsu, S ;
Noronha, A ;
Manoharan, M ;
Akira, S ;
de Fougerolles, A ;
Endres, S ;
Hartmann, G .
NATURE MEDICINE, 2005, 11 (03) :263-270
[10]   Regulation of Adaptive Immunity by the Innate Immune System [J].
Iwasaki, Akiko ;
Medzhitov, Ruslan .
SCIENCE, 2010, 327 (5963) :291-295