Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa
Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium.
Vyšlo v časopise:
Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa. PLoS Pathog 6(5): e32767. doi:10.1371/journal.ppat.1000902
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000902
Souhrn
Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium.
Zdroje
1. NataroJP
KaperJB
1998 Diarrheagenic Escherichia coli. Clin Microbiol Rev 11 142 201
2. Fagundes-NetoU
AndradeJABd
1999 Acute Diarrhea and Malnutrition: Lethality Risk in Hospitalized Infants. J Am Coll Nutr 18 303 308
3. VilchezS
ReyesD
PaniaguaM
BucardoF
MollbyR
2009 Prevalence of diarrhoeagenic Escherichia coli in children from Leon, Nicaragua. J Med Microbiol 58 630 637
4. Gonzalez GarciaEA
2002 Animal health and foodborne pathogens: enterohaemorrhagic O157:H7 strains and other pathogenic Escherichia coli virotypes (EPEC, ETEC, EIEC, EHEC). Pol J Vet Sci 5 103 115
5. KarchH
TarrPI
BielaszewskaM
2005 Enterohaemorrhagic Escherichia coli in human medicine. International Journal of Medical Microbiology 295 405 418
6. YoonJW
HovdeCJ
2008 All blood, no stool: enterohemorrhagic Escherichia coli O157:H7 infection. J Vet Sci 9 219 231
7. WalesAD
WoodwardMJ
PearsonGR
2005 Attaching-effacing bacteria in animals. J Comp Pathol 132 1 26
8. VallanceBA
FinlayBB
2000 Exploitation of host cells by enteropathogenic Escherichia coli. Proc Natl Acad Sci U S A 97 8799 8806
9. LuperchioSA
SchauerDB
2001 Molecular pathogenesis of Citrobacter rodentium and transmissible murine colonic hyperplasia. Microbes Infect 3 333 340
10. MundyR
MacDonaldTT
DouganG
FrankelG
WilesS
2005 Citrobacter rodentium of mice and man. Cell Microbiol 7 1697 1706
11. BryL
BrennerMB
2004 Critical Role of T Cell-Dependent Serum Antibody, but Not the Gut-Associated Lymphoid Tissue, for Surviving Acute Mucosal Infection with Citrobacter rodentium, an Attaching and Effacing Pathogen. J Immunol 172 433 441
12. MaaserC
HousleyMP
IimuraM
SmithJR
VallanceBA
2004 Clearance of Citrobacter rodentium Requires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies. Infect Immun 72 3315 3324
13. IimuraM
GalloRL
HaseK
MiyamotoY
EckmannL
2005 Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol 174 4901 4907
14. VallanceBA
DijkstraG
QiuB
van der WaaijLA
van GoorH
2004 Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity. Am J Physiol Gastrointest Liver Physiol 287 G865 874
15. LindenSK
SuttonP
KarlssonNG
KorolikV
McGuckinMA
2008 Mucins in the mucosal barrier to infection. Mucosal Immunol 1 183 197
16. DharmaniP
SrivastavaV
Kissoon-SinghV
ChadeeK
2009 Role of Intestinal Mucins in Innate Host Defense Mechanisms against Pathogens. Journal of Innate Immunity 1 123 135
17. Lievin-Le MoalV
ServinAL
2006 The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota. Clin Microbiol Rev 19 315 337
18. McAuleyJL
LindenSK
PngCW
KingRM
PenningtonHL
2007 MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest 117 2313 2324
19. LindenSK
FlorinTH
McGuckinMA
2008 Mucin dynamics in intestinal bacterial infection. PLoS One 3 e3952
20. MackDR
MichailS
WeiS
McDougallL
HollingsworthMA
1999 Probiotics inhibit enteropathogenic E.†coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol Gastrointest Liver Physiol 276 G941 950
21. AllenA
HuttonDA
PearsonJP
1998 The MUC2 gene product: a human intestinal mucin. The International Journal of Biochemistry & Cell Biology 30 797 801
22. Van KlinkenBJ-W
EinerhandAWC
DuitsLA
MakkinkMK
TytgatKMAJ
1999 Gastrointestinal expression and partial cDNA cloning of murine Muc2. Am J Physiol Gastrointest Liver Physiol 276 G115 124
23. SpecianRD
OliverMG
1991 Functional biology of intestinal goblet cells. Am J Physiol 260 C183 193
24. JohanssonMEV
ThomssonKA
HanssonGC
2009 Proteomic Analyses of the Two Mucus Layers of the Colon Barrier Reveal That Their Main Component, the Muc2 Mucin, Is Strongly Bound to the Fcgbp Protein. Journal of Proteome Research 8 3549 3557
25. AtumaC
StrugalaV
AllenA
HolmL
2001 The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol 280 G922 929
26. MatsuoK
OtaH
AkamatsuT
SugiyamaA
KatsuyamaT
1997 Histochemistry of the surface mucous gel layer of the human colon. Gut 40 782 789
27. JohanssonME
PhillipsonM
PeterssonJ
VelcichA
HolmL
2008 The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A 105 15064 15069
28. VelcichA
YangW
HeyerJ
FragaleA
NicholasC
2002 Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295 1726 1729
29. Van der SluisM
De KoningBA
De BruijnAC
VelcichA
MeijerinkJP
2006 Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131 117 129
30. YangK
PopovaNV
YangWC
LozonschiI
TadesseS
2008 Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation. Cancer Res 68 7313 7322
31. YangW
VelcichA
LozonschiI
LiangJ
NicholasC
2005 Inactivation of p21WAF1/cip1 enhances intestinal tumor formation in Muc2−/− mice. Am J Pathol 166 1239 1246
32. HeazlewoodCK
CookMC
EriR
PriceGR
TauroSB
2008 Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med 5 e54
33. DeplanckeB
GaskinsHR
2001 Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. Am J Clin Nutr 73 1131S 1141S
34. SwidsinskiA
Loening-BauckeV
TheissigF
EngelhardtH
BengmarkS
2007 Comparative study of the intestinal mucus barrier in normal and inflamed colon. Gut 56 343 350
35. WilesS
PickardKM
PengK
MacDonaldTT
FrankelG
2006 In Vivo Bioluminescence Imaging of the Murine Pathogen Citrobacter rodentium. Infect Immun 74 5391 5396
36. IshigameH
KakutaS
NagaiT
KadokiM
NambuA
2009 Differential Roles of Interleukin-17A and -17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses. Immunity 30 108 119
37. ZhengY
ValdezPA
DanilenkoDM
HuY
SaSM
2008 Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14 282 289
38. ManganPR
HarringtonLE
O'QuinnDB
HelmsWS
BullardDC
2006 Transforming growth factor-[beta] induces development of the TH17 lineage. Nature 441 231 234
39. BryL
BriglM
BrennerMB
2006 CD4+-T-Cell Effector Functions and Costimulatory Requirements Essential for Surviving Mucosal Infection with Citrobacter rodentium. Infect Immun 74 673 681
40. NagaiT
AbeA
SasakawaC
2005 Targeting of Enteropathogenic Escherichia coli EspF to Host Mitochondria Is Essential for Bacterial Pathogenesis: CRITICAL ROLE OF THE 16TH LEUCINE RESIDUE IN EspF. J Biol Chem 280 2998 3011
41. TorchinskyMB
GaraudeJ
MartinAP
BlanderJM
2009 Innate immune recognition of infected apoptotic cells directs TH17 cell differentiation. Nature 458 78 82
42. GibsonDL
MaC
RosenbergerCM
BergstromKS
ValdezY
2008 Toll-like receptor 2 plays a critical role in maintaining mucosal integrity during Citrobacter rodentium-induced colitis. Cell Microbiol 10 388 403
43. DengW
PuenteJL
GruenheidS
LiY
VallanceBA
2004 Dissecting virulence: systematic and functional analyses of a pathogenicity island. Proc Natl Acad Sci U S A 101 3597 3602
44. BergstromKS
GuttmanJA
RumiM
MaC
BouzariS
2008 Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen. Infect Immun 76 796 811
45. SmithCJ
KaperJB
MackDR
1995 Intestinal mucin inhibits adhesion of human enteropathogenic Escherichia coli to HEp-2 cells. J Pediatr Gastroenterol Nutr 21 269 276
46. DengW
VallanceBA
LiY
PuenteJL
FinlayBB
2003 Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization and colonic hyperplasia in mice. Mol Microbiol 48 95 115
47. VallanceBA
DengW
De GradoM
ChanC
JacobsonK
2002 Modulation of inducible nitric oxide synthase expression by the attaching and effacing bacterial pathogen citrobacter rodentium in infected mice. Infect Immun 70 6424 6435
48. Meyer-HoffertU
HornefMW
Henriques-NormarkB
AxelssonLG
MidtvedtT
2008 Secreted enteric antimicrobial activity localises to the mucus surface layer. Gut 57 764 771
49. MantleM
HusarSD
1993 Adhesion of Yersinia enterocolitica to purified rabbit and human intestinal mucin. Infect Immun 61 2340 2346
50. Lievin-Le MoalV
ServinAL
Coconnier-PolterMH
2005 The increase in mucin exocytosis and the upregulation of MUC genes encoding for membrane-bound mucins induced by the thiol-activated exotoxin listeriolysin O is a host cell defence response that inhibits the cell-entry of Listeria monocytogenes. Cell Microbiol 7 1035 1048
51. EnssML
MullerH
Schmidt-WittigU
KownatzkiR
CoenenM
1996 Effects of perorally applied endotoxin on colonic mucins of germfree rats. Scand J Gastroenterol 31 868 874
52. Caballero-FrancoC
KellerK
De SimoneC
ChadeeK
2007 The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 292 G315 322
53. TytgatKM
BullerHA
OpdamFJ
KimYS
EinerhandAW
1994 Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin. Gastroenterology 107 1352 1363
54. TytgatKM
OpdamFJ
EinerhandAW
BullerHA
DekkerJ
1996 MUC2 is the prominent colonic mucin expressed in ulcerative colitis. Gut 38 554 563
55. RongM
RossiEA
ZhangJ
McNeerRR
van den BrandeJM
2005 Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: implications for Muc4/SMC function. J Cell Physiol 202 275 284
56. DasB
CashMN
HandAR
ShivazadA
GrieshaberSS
Tissue Distibution of Murine Muc19/Smgc Gene Products. J Histochem Cytochem 58 141 156
57. EscandeF
PorchetN
BernigaudA
PetitprezD
AubertJ-P
2004 The mouse secreted gel-forming mucin gene cluster. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1676 240 250
58. LuppC
RobertsonML
WickhamME
SekirovI
ChampionOL
2007 Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2 204
59. HoffmannC
HillDA
MinkahN
KirnT
TroyA
2009 Community-Wide Response of the Gut Microbiota to Enteropathogenic Citrobacter rodentium Infection Revealed by Deep Sequencing. Infect Immun 77 4668 4678
60. KhanMA
BouzariS
MaC
RosenbergerCM
BergstromKS
2008 Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium. Infect Immun 76 1410 1422
61. GrysTE
WaltersLL
WelchRA
2006 Characterization of the StcE protease activity of Escherichia coli O157:H7. J Bacteriol 188 4646 4653
62. HooperLV
2009 Do symbiotic bacteria subvert host immunity? Nat Rev Microbiol 7 367 374
63. ViswanathanVK
KoutsourisA
LukicS
PilkintonM
SimonovicI
2004 Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function. Infect Immun 72 3218 3227
64. GunningRF
WalesAD
PearsonGR
DoneE
CooksonAL
2001 Attaching and effacing lesions in the intestines of two calves associated with natural infection with Escherichia coli O26:H11. Vet Rec 148 780 782
65. MaC
WickhamME
GuttmanJA
DengW
WalkerJ
2006 Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map). Cellular Microbiology 8 1669 1686
66. DannSM
SpehlmannME
HammondDC
IimuraM
HaseK
2008 IL-6-Dependent Mucosal Protection Prevents Establishment of a Microbial Niche for Attaching/Effacing Lesion-Forming Enteric Bacterial Pathogens. J Immunol 180 6816 6826
67. GuttmanJA
LiY
WickhamME
DengW
VoglAW
2006 Attaching and effacing pathogen-induced tight junction disruption in vivo. Cellular Microbiology 8 634 645
68. StecherBr
RobbianiR
WalkerAW
WestendorfAM
BarthelM
2007 Salmonella enterica Serovar Typhimurium Exploits Inflammation to Compete with the Intestinal Microbiota. PLoS Biol 5 e244
69. WilesS
PickardKM
PengK
MacDonaldTT
FrankelG
2006 In vivo bioluminescence imaging of the murine pathogen Citrobacter rodentium. Infect Immun 74 5391 5396
70. SmirnovaMG
GuoL
BirchallJP
PearsonJP
2003 LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells. Cell Immunol 221 42 49
71. IwashitaJ
SatoY
SugayaH
TakahashiN
SasakiH
2003 mRNA of MUC2 is stimulated by IL-4, IL-13 or TNF-[alpha] through a mitogen-activated protein kinase pathway in human colon cancer cells. Immunol Cell Biol 81 275 282
72. PlaisancieP
BarceloA
MoroF
ClaustreJ
ChayvialleJ-A
1998 Effects of neurotransmitters, gut hormones, and inflammatory mediators on mucus discharge in rat colon. Am J Physiol Gastrointest Liver Physiol 275 G1073 1084
73. KimS
NadelJA
2004 Role of neutrophils in mucus hypersecretion in COPD and implications for therapy. Treat Respir Med 3 147 159
74. LebeisSL
BommariusB
ParkosCA
ShermanMA
KalmanD
2007 TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium. J Immunol 179 566 577
75. GibsonDL
MaC
BergstromKS
HuangJT
ManC
2008 MyD88 signalling plays a critical role in host defence by controlling pathogen burden and promoting epithelial cell homeostasis during Citrobacter rodentium-induced colitis. Cell Microbiol 10 618 631
76. ConlinVS
WuX
NguyenC
DaiC
VallanceBA
2009 Vasoactive Intestinal Peptide Ameliorates Intestinal Barrier Disruption Associated with Citrobacter rodentium-induced Colitis. Am J Physiol Gastrointest Liver Physiol
77. LindénSK
ShengYH
EveryAL
MilesKM
SkoogEC
2009 MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy. PLoS Pathog 5 e1000617
78. HoeblerC
GaudierE
De CoppetP
RivalM
CherbutC
2006 MUC Genes Are Differently Expressed During Onset and Maintenance of Inflammation in Dextran Sodium Sulfate-Treated Mice. Digestive Diseases and Sciences 51 381 389
79. HasnainSZ
WangH
GhiaJ-E
HaqN
DengY
Mucin Gene Deficiency in Mice Impairs Host Resistance to an Enteric Parasitic Infection. Gastroenterology In Press, Accepted Manuscript
80. ShamesSR
AuweterSD
FinlayBB
2009 Co-evolution and exploitation of host cell signaling pathways by bacterial pathogens. The International Journal of Biochemistry & Cell Biology 41 380 389
81. ChessaD
WinterMG
JakominM
B‰umlerAJ
2009 Salmonella enterica serotype Typhimurium Std fimbriae bind terminal α-03B1;(1,2)fucose residues in the cecal mucosa. Molecular Microbiology 71 864 875
82. VimalDB
KhullarM
GuptaS
GangulyNK
2000 Intestinal mucins: the binding sites for Salmonella typhimurium. Mol Cell Biochem 204 107 117
83. MantleM
RomboughC
1993 Growth in and breakdown of purified rabbit small intestinal mucin by Yersinia enterocolitica. Infect Immun 61 4131 4138
84. StecherBr
BarthelM
SchlumbergerMC
HaberliL
RabschW
2008 Motility allows S. Typhimurium to benefit from the mucosal defence. Cellular Microbiology 10 1166 1180
85. ChadeeK
KellerK
ForstnerJ
InnesDJ
RavdinJI
1991 Mucin and nonmucin secretagogue activity of Entamoeba histolytica and cholera toxin in rat colon. Gastroenterology 100 986 997
86. LidellME
MoncadaDM
ChadeeK
HanssonGC
2006 Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel. Proc Natl Acad Sci U S A 103 9298 9303
87. MoncadaD
KellerK
ChadeeK
2003 Entamoeba histolytica cysteine proteinases disrupt the polymeric structure of colonic mucin and alter its protective function. Infect Immun 71 838 844
88. KhanMA
MaC
KnodlerLA
ValdezY
RosenbergerCM
2006 Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice. Infect Immun 74 2522 2536
89. DeanP
MarescaM
SchullerS
PhillipsAD
KennyB
2006 Potent diarrheagenic mechanism mediated by the cooperative action of three enteropathogenic Escherichia coli-injected effector proteins. Proc Natl Acad Sci U S A 103 1876 1881
90. BrownNF
VallanceBA
CoombesBK
ValdezY
CoburnBA
2005 Salmonella Pathogenicity Island 2 Is Expressed Prior to Penetrating the Intestine. PLoS Pathog 1 e32
91. AmannRI
KrumholzL
StahlDA
1990 Fluorescent-oligonucleotide probing of whole cells for determinative, phylogenetic, and environmental studies in microbiology. J Bacteriol 172 762 770
92. TurnerJ
ChoY
DinhNN
WaringAJ
LehrerRI
1998 Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 42 2206 2214
93. BarthelM
HapfelmeierS
Quintanilla-MartinezL
KremerM
RohdeM
2003 Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun 71 2839 2858
94. RheeSJ
WalkerWA
CherayilBJ
2005 Developmentally Regulated Intestinal Expression of IFN-{gamma} and Its Target Genes and the Age-Specific Response to Enteric Salmonella Infection. J Immunol 175 1127 1136
95. NenciA
BeckerC
WullaertA
GareusR
van LooG
2007 Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446 557 561
96. MarriottI
GrayDL
RatiDM
FowlerVGJr
StryjewskiME
2005 Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. Bone 37 504 512
97. SugawaraI
YamadaH
LiC
MizunoS
TakeuchiO
2003 Mycobacterial Infection in TLR2 and TLR6 Knockout Mice. MICROBIOLOGY and IMMUNOLOGY 47 327 336
98. GodinezI
HanedaT
RaffatelluM
GeorgeMD
PaixaoTA
2008 T Cells Help To Amplify Inflammatory Responses Induced by Salmonella enterica Serotype Typhimurium in the Intestinal Mucosa. Infect Immun 76 2008 2017
99. HappelKI
LockhartEA
MasonCM
PorrettaE
KeoshkerianE
2005 Pulmonary Interleukin-23 Gene Delivery Increases Local T-Cell Immunity and Controls Growth of Mycobacterium tuberculosis in the Lungs. Infect Immun 73 5782 5788
100. BrandS
BeigelF
OlszakT
ZitzmannK
EichhorstST
2006 IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 290 G827 838
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