Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4-and mTOR-Dependent Manner

被引:46
作者
Waller, Tobias [1 ,2 ]
Kesper, Laura [1 ]
Hirschfeld, Josefine [1 ,2 ]
Dommisch, Henrik [2 ,3 ]
Koelpin, Johanna [1 ]
Oldenburg, Johannes [4 ]
Uebele, Julia [1 ,5 ]
Hoerauf, Achim [1 ]
Deschner, James [6 ]
Jepsen, Soeren [2 ]
Bekeredjian-Ding, Isabelle [1 ,5 ]
机构
[1] Univ Hosp Bonn, IMMIP, Bonn, Germany
[2] Univ Hosp Bonn, Ctr Dent & Oral Med, Dept Periodontol Operat & Prevent Dent, Bonn, Germany
[3] Charite, Inst Dent & Oral Med, Dept Periodontol & Synopt Dent, Berlin, Germany
[4] Univ Bonn, Inst Expt Hematol & Transfus Med, Bonn, Germany
[5] Paul Ehrlich Inst, Div Microbiol, Langen, Germany
[6] Univ Hosp Bonn, Ctr Dent & Oral Med, Dept Expt Dento Maxillo Facial Med, Bonn, Germany
关键词
LIPOPOLYSACCHARIDE PREPARATION; ENDOTOXIN TOLERANCE; MAMMALIAN TARGET; TNF-ALPHA; LIPOPROTEIN; ACTIVATION; TLR2; CD14; LPS; MACROPHAGES;
D O I
10.1128/IAI.01390-15
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA.dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness to P. gingivalis; full reactivity to P. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV-mediated TNF tolerance: only blockade of TLR4-and not of TLR2-restores responsiveness to P. gingivalis. Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response.
引用
收藏
页码:1194 / 1204
页数:11
相关论文
共 63 条
[1]   Lipopolysaccharide preparation extracted from Porphyromonas gingivalis lipoprotein-deficient mutant shows a marked decrease in Toll-like receptor 2-mediated signaling [J].
Asai, Y ;
Hashimoto, M ;
Fletcher, HM ;
Miyake, K ;
Akira, S ;
Ogawa, T .
INFECTION AND IMMUNITY, 2005, 73 (04) :2157-2163
[2]  
Bai D, 2014, PATHOG DIS
[3]   Rapamycin enhances LPS induction of tissue factor and tumor necrosis factor-α expression in macrophages by reducing IL-10 expression [J].
Baker, Alyson K. ;
Wang, Ruipeng ;
Mackman, Nigel ;
Luyendyk, James P. .
MOLECULAR IMMUNOLOGY, 2009, 46 (11-12) :2249-2255
[4]   Staphylococcus aureus protein A triggers T cell-independent B cell proliferation by sensitizing B cells for TLR2 ligands [J].
Bekeredjian-Ding, Isabelle ;
Inamura, Seiichi ;
Giese, Thomas ;
Moll, Hermann ;
Endres, Stefan ;
Sing, Andreas ;
Zaehringer, Ulrich ;
Hartmann, Gunther .
JOURNAL OF IMMUNOLOGY, 2007, 178 (05) :2803-2812
[5]   Poke Weed Mitogen Requires Toll-Like Receptor Ligands for Proliferative Activity in Human and Murine B Lymphocytes [J].
Bekeredjian-Ding, Isabelle ;
Foermer, Sandra ;
Kirschning, Carsten J. ;
Parcina, Marijo ;
Heeg, Klaus .
PLOS ONE, 2012, 7 (01)
[6]   THE IMMUNOBIOLOGY OF TOLL-LIKE RECEPTOR 4 AGONISTS: FROM ENDOTOXIN TOLERANCE TO IMMUNOADJUVANTS [J].
Bohannon, Julia K. ;
Hernandez, Antonio ;
Enkhbaatar, Perenlei ;
Adams, William L. ;
Sherwood, Edward R. .
SHOCK, 2013, 40 (06) :451-462
[7]   A NEGATIVE STAINING METHOD FOR HIGH RESOLUTION ELECTRON MICROSCOPY OF VIRUSES [J].
BRENNER, S ;
HORNE, RW .
BIOCHIMICA ET BIOPHYSICA ACTA, 1959, 34 (01) :103-110
[8]   Cutting edge:: TLR2 is required for the innate response to Porphyromonas gingivalis:: activation leads to bacterial persistence and TLR2 deficiency attenuates induced alveolar bone resorption [J].
Burns, Elia ;
Bachrach, Gilad ;
Shapira, Lior ;
Nussbaum, Gabriel .
JOURNAL OF IMMUNOLOGY, 2006, 177 (12) :8296-8300
[9]   Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3) K-mTOR-p70S6K pathway [J].
Cao, Weiping ;
Manicassamy, Santhakumar ;
Tang, Hua ;
Kasturi, Sudhir Pai ;
Pirani, Ali ;
Murthy, Niren ;
Pulendran, Bali .
NATURE IMMUNOLOGY, 2008, 9 (10) :1157-1164
[10]   Activation of TLR2 and TLR4 by minimally modified low-density lipoprotein in human macrophages and monocytes triggers the inflammatory response [J].
Chavez-Sanchez, L. ;
Madrid-Miller, A. ;
Chavez-Rueda, K. ;
Legorreta-Haquet, M. V. ;
Tesoro-Cruz, E. ;
Blanco-Favela, F. .
HUMAN IMMUNOLOGY, 2010, 71 (08) :737-744