The Danger Signal S100B Integrates Pathogen– and Danger–Sensing Pathways to Restrain Inflammation
Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen– and danger–sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen–induced inflammation and a pathogen–sensing mechanism resolves danger–induced inflammation.
Vyšlo v časopise:
The Danger Signal S100B Integrates Pathogen– and Danger–Sensing Pathways to Restrain Inflammation. PLoS Pathog 7(3): e32767. doi:10.1371/journal.ppat.1001315
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001315
Souhrn
Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen– and danger–sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen–induced inflammation and a pathogen–sensing mechanism resolves danger–induced inflammation.
Zdroje
1. GallucciS
MatzingerP
2001 Danger signals: SOS to the immune system. Curr Opin Immunol 13 114 119
2. JanewayCAJr
MedzhitovR
2002 Innate immune recognition. Annu Rev Immunol 20 197 216
3. DonatoR
2007 RAGE: a single receptor for several ligands and different cellular responses: the case of certain S100 proteins. Curr Mol Med 7 711 724
4. SchmidtAM
YanSD
YanSF
SternDM
2001 The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 108 949 955
5. SparveroLJ
Asafu-AdjeiD
KangR
TangD
AminN
2009 RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 7 17
6. LinL
2006 RAGE on the Toll Road? Cell Mol Immunol 3 351 358
7. O'NeillLA
2006 How Toll-like receptors signal: what we know and what we don't know. Curr Opin Immunol 18 3 9
8. ChenGY
TangJ
ZhengP
LiuY
2009 CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323 1722 1725
9. LiuY
ChenGY
ZhengP
2009 CD24-Siglec G/10 discriminates danger- from pathogen-associated molecular patterns. Trends Immunol 30 557 561
10. SitkovskyMV
OhtaA
2005 The ‘danger’ sensors that STOP the immune response: the A2 adenosine receptors? Trends Immunol 26 299 304
11. BianchiME
2009 HMGB1 loves company. J Leukoc Biol 86 573 576
12. DonatoR
SorciG
RiuzziF
ArcuriC
BianchiR
2009 S100B's double life: intracellular regulator and extracellular signal. Biochim Biophys Acta 1793 1008 1022
13. GebhardtC
RiehlA
DurchdewaldM
NemethJ
FurstenbergerG
2008 RAGE signaling sustains inflammation and promotes tumor development. J Exp Med 205 275 285
14. KaleaAZ
ReinigerN
YangH
ArrieroM
SchmidtAM
2009 Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene. Faseb J 23 1766 1774
15. LeclercE
FritzG
WeibelM
HeizmannCW
GalichetA
2007 S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. J Biol Chem 282 31317 31331
16. OstendorpT
LeclercE
GalichetA
KochM
DemlingN
2007 Structural and functional insights into RAGE activation by multimeric S100B. Embo J 26 3868 3878
17. LeclercE
FritzG
VetterSW
HeizmannCW
2009 Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta 1793 993 1007
18. IvanovS
DragoiAM
WangX
DallacostaC
LoutenJ
2007 A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110 1970 1981
19. TianJ
AvalosAM
MaoSY
ChenB
SenthilK
2007 Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8 487 496
20. YanaiH
BanT
WangZ
ChoiMK
KawamuraT
2009 HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462 99 103
21. ClynesR
MoserB
YanSF
RamasamyR
HeroldK
2007 Receptor for AGE (RAGE): weaving tangled webs within the inflammatory response. Curr Mol Med 7 743 751
22. van ZoelenMA
SchoutenM
de VosAF
FlorquinS
MeijersJC
2009 The receptor for advanced glycation end products impairs host defense in pneumococcal pneumonia. J Immunol 182 4349 4356
23. SegalBH
2009 Aspergillosis. N Engl J Med 360 1870 1884
24. AimaniandaV
BayryJ
BozzaS
KniemeyerO
PerruccioK
2009 Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 460 1117 1121
25. RomaniL
FallarinoF
De LucaA
MontagnoliC
D'AngeloC
2008 Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 451 211 215
26. ChavakisT
BierhausA
Al-FakhriN
SchneiderD
WitteS
2003 The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 198 1507 1515
27. ManfrediAA
CapobiancoA
EspositoA
De CobelliF
CanuT
2008 Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes. J Immunol 180 2270 2275
28. MoserB
DesaiDD
DownieMP
ChenY
YanSF
2007 Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo. J Immunol 179 8051 8058
29. ZelanteT
De LucaA
BonifaziP
MontagnoliC
BozzaS
2007 IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol 37 2695 2706
30. BonifaziP
D'AngeloC
ZagarellaS
ZelanteT
BozzaS
2010 Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis. Mucosal Immunol 3 193 205
31. DonatoR
2003 Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 60 540 551
32. HuttunenHJ
Kuja-PanulaJ
SorciG
AgnelettiAL
DonatoR
2000 Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 275 40096 40105
33. HreggvidsdottirHS
OstbergT
WahamaaH
SchierbeckH
AvebergerAC
2009 The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol 86 655 662
34. BellocchioS
MorettiS
PerruccioK
FallarinoF
BozzaS
2004 TLRs govern neutrophil activity in aspergillosis. J Immunol 173 7406 7415
35. MorettiS
BellocchioS
BonifaziP
BozzaS
ZelanteT
2008 The contribution of PARs to inflammation and immunity to fungi. Mucosal Immunol 1 156 168
36. SahayB
PatseyRL
EggersCH
SalazarJC
RadolfJD
2009 CD14 signaling restrains chronic inflammation through induction of p38-MAPK/SOCS-dependent tolerance. PLoS Pathog 5 e1000687
37. ShaQ
Truong-TranAQ
PlittJR
BeckLA
SchleimerRP
2004 Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol 31 358 364
38. BonizziG
KarinM
2004 The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25 280 288
39. PopovicPJ
DeMarcoR
LotzeMT
WinikoffSE
BartlettDL
2006 High mobility group B1 protein suppresses the human plasmacytoid dendritic cell response to TLR9 agonists. J Immunol 177 8701 8707
40. CollisonKS
ParharRS
SalehSS
MeyerBF
KwaasiAA
2002 RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). J Leukoc Biol 71 433 444
41. ChaiLY
KullbergBJ
VonkAG
WarrisA
CambiA
2009 Modulation of Toll-like receptor 2 (TLR2) and TLR4 responses by Aspergillus fumigatus. Infect Immun 77 2184 2192
42. BierhausA
HumpertPM
MorcosM
WendtT
ChavakisT
2005 Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 83 876 886
43. HuttunenHJ
FagesC
RauvalaH
1999 Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-kappaB require the cytoplasmic domain of the receptor but different downstream signaling pathways. J Biol Chem 274 19919 19924
44. AdamiC
BianchiR
PulaG
DonatoR
2004 S100B-stimulated NO production by BV-2 microglia is independent of RAGE transducing activity but dependent on RAGE extracellular domain. Biochim Biophys Acta 1742 169 177
45. KajavaAV
VasselonT
2010 A network of hydrogen bonds on the surface of TLR2 controls ligand positioning and cell signaling. J Biol Chem 6227 6234
46. HeizmannCW
FritzG
SchaferBW
2002 S100 proteins: structure, functions and pathology. Front Biosci 7 d1356 1368
47. GuiducciC
OttG
ChanJH
DamonE
CalacsanC
2006 Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J Exp Med 203 1999 2008
48. HondaK
OhbaY
YanaiH
NegishiH
MizutaniT
2005 Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434 1035 1040
49. Ramirez-OrtizZG
SpechtCA
WangJP
LeeCK
BartholomeuDC
2008 Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA. Infect Immun 76 2123 2129
50. BozzaS
PerruccioK
MontagnoliC
GazianoR
BellocchioS
2003 A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102 3807 3814
51. KarikoK
NiH
CapodiciJ
LamphierM
WeissmanD
2004 mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 279 12542 12550
52. AksoyE
ZouainCS
VanhoutteF
FontaineJ
PavelkaN
2005 Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in dendritic cells. J Biol Chem 280 277 283
53. CavassaniKA
IshiiM
WenH
SchallerMA
LincolnPM
2008 TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J Exp Med 205 2609 2621
54. CastetsF
GriffinWS
MarksA
Van EldikLJ
1997 Transcriptional regulation of the human S100 beta gene. Brain Res Mol Brain Res 46 208 216
55. CaiW
HeJC
ZhuL
LuC
VlassaraH
2006 Advanced glycation end product (AGE) receptor 1 suppresses cell oxidant stress and activation signaling via EGF receptor. Proc Natl Acad Sci U S A 103 13801 13806
56. VivesV
AlonsoG
SolalAC
JoubertD
LegraverendC
2003 Visualization of S100B-positive neurons and glia in the central nervous system of EGFP transgenic mice. J Comp Neurol 457 404 419
57. YouY
RicherEJ
HuangT
BrodySL
2002 Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population. Am J Physiol Lung Cell Mol Physiol 283 L1315 1321
58. SorciG
RiuzziF
AgnelettiAL
MarchettiC
DonatoR
2003 S100B inhibits myogenic differentiation and myotube formation in a RAGE-independent manner. Mol Cell Biol 23 4870 4881
59. SoderbergO
GullbergM
JarviusM
RidderstraleK
LeuchowiusKJ
2006 Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods 3 995 1000
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2011 Číslo 3
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- A Toxin that Hijacks the Host Ubiquitin Proteolytic System
- Invasive Extravillous Trophoblasts Restrict Intracellular Growth and Spread of
- Blood Meal-Derived Heme Decreases ROS Levels in the Midgut of and Allows Proliferation of Intestinal Microbiota
- Metabolite Cross-Feeding Enhances Virulence in a Model Polymicrobial Infection