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156 results on '"Crepin, Valerie F."'

5. A type III effector antagonizes death receptor signalling during bacterial gut infection

Author

Pearson, Jaclyn S., Giogha, Cristina, Ong, Sze Ying, Kennedy, Catherine L., Kelly, Michelle, Robinson, Keith S., Lung, Tania Wong Fok, Mansell, Ashley, Riedmaier, Patrice, Oates, Clare V.L., Zaid, Ali, Muhlen, Sabrina, Crepin, Valerie F., Marches, Olivier, Ang, Ching-Seng, Williamson, Nicholas A., O'Reilly, Lorraine A., Bankovacki, Aleksandra, Nachbur, Ueli, Infusini, Giuseppe, Webb, Andrew I., Silke, John, Strasser, Andreas, Frankel, Gad, and Hartland, Elizabeth L.

Subjects
Stomach diseases -- Physiological aspects, Bacterial infections -- Research, Microbiology -- Research, Cell receptors -- Physiological aspects, Pathogenic microorganisms -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Successful infection by enteric bacterial pathogens depends on the ability of the bacteria to colonize the gut, replicate in host tissues and disseminate to other hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and enterohaemorrhagic (EPEC and EHEC, respectively) Escherichia coli use a type III secretion system (T3SS) to deliver virulence effector proteins into host cells during infection that promote colonization and interfere with antimicrobial host responses (1-3). Here we report that the T3SS effector NleB1 from EPEC binds to host cell death-domain-containing proteins and thereby inhibits death receptor signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as binding partners of NleB1. NleB1 expressed ectopically or injected by the bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical death-inducing signalling complex (DISC) and proteolytic activation of caspase-8, an essential step in death-receptor-induced apoptosis. This inhibition depended on the N-acetylglucosamine transferase activity of NleB1, which specifically modified Arg 117 in the death domain of FADD. The importance of the death receptor apoptotic pathway to host defence was demonstrated using mice deficient in the FAS signalling pathway, which showed delayed clearance of the EPEC-like mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB mutant. The activity of NleB suggests that EPEC and other attaching and effacing pathogens antagonize death-receptor-induced apoptosis of infected cells, thereby blocking a major antimicrobial host response., Members of the death receptor family such as FAS and TNFR1 contain an intracellular death domain and require caspase-8 for the activation of effector caspases and consequent cell death by [...]

Published
2013

6. N-terminal type III secretion signal of enteropathogenic Escherichia coli translocator proteins

Author

Munera, Diana, Crepin, Valerie F., Marches, Olivier, and Frankel, Gad

Subjects
Escherichia coli -- Physiological aspects, Escherichia coli -- Genetic aspects, Bacterial proteins -- Genetic aspects, Translocation (Genetics) -- Physiological aspects, Biological sciences
Abstract

We report that the N terminus of the type III secretion system translocator proteins EspB, EspD, and EspA mediate protein secretion and translocation from wild-type enteropathogenic Escherichia coli and hypersecretion from sepL and sepD mutants. EspA containing the translocation signal of Map and Tir containing the secretion signal of EspA are biologically active. doi: 10.1128/JB.00046-10

Published
2010

7. The Citrobacter rodentium genome sequence reveals convergent evolution with human pathogenic Escherichia coli

Author

Petty, Nicola K., Bulgin, Richard, Crepin, Valerie F., Cerdeno-Tarraga, Ana M., Schroeder, Gunnar N., Quail, Michael A., Lennard, Nicola, Corton, Craig, Barron, Andrew, Clark, Louise, Toribio, Ana L., Parkhill, Julian, Dougan, Gordon, Frankel, Gad, and Thomson, Nicholas R.

Subjects
Convergence (Biology) -- Research, Escherichia coli -- Genetic aspects, Biological sciences
Abstract

Citrobacter rodentium (formally Citrobacterfreundii biotype 4280) is a highly infectious pathogen that causes colitis and transmissible colonic hyperplasia in mice. In common with enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), C. rodentium exploits a type III secretion system (T3SS) to induce attaching and effacing (A/E) lesions that are essential for virulence. Here, we report the fully annotated genome sequence of the 5.3-Mb chromosome and four plasmids harbored by C. rodentium strain ICC168. The genome sequence revealed key information about the phylogeny of C. rodentium and identified 1,585 C. rodentium-specific (without orthologues in EPEC or EHEC) coding sequences, 10 prophage-like regions, and 17 genomic islands, including the locus for enterocyte effacement (LEE) region, which encodes a T3SS and effector proteins. Among the 29 T3SS effectors found in C. rodentium are all 22 of the core effectors of EPEC strain E2348/69. In addition, we identified a novel C. rodentium effector, named EspS. C. rodentium harbors two type VI secretion systems (T6SS) (CTS1 and CTS2), while EHEC contains only one T6SS (EHS). Our analysis suggests that C. rodentium and EPEC/EHEC have converged on a common host infection strategy through access to a common pool of mobile DNA and that C. rodentium has lost gene functions associated with a previous pathogenic niche. doi: 10.1128/JB.01144-09

Published
2010

8. Identification of amino acid residues within the N-terminal domain of EspA that play a role in EspA filament biogenesis and function

Author

Singh, Mona P., Shaw, Robert K., Knutton, Stuart, Pallen, Mark J., Crepin, Valerie F., and Frankel, Gad

Subjects
Escherichia coli -- Physiological aspects, Bacterial proteins -- Properties, Biological sciences
Abstract

Enteropathogenic Escherichia coli employs a filamentous type III secretion system, made by homopolymerization of the translocator protein EspA. In this study, we have shown that the N-terminal region of EspA has a role in EspA's protein stability, interaction with the CesAB chaperone, and filament biogenesis and function.

Published
2008

9. Polarity of enteropathogenic Escherichia coli EspA filament assembly and protein secretion

Author

Crepin, Valerie F., Shaw, Robert, Abe, Cecilia M., Knutton, Stuart, and Frankel, Gad

Subjects
Bacteriology -- Research, Proteins -- Research, Escherichia coli -- Research, Biological sciences
Abstract

Type III secretion systems (TTSS) are sophisticated macromolecular structures that play an imperative role in bacterial infections and human disease. The TTSS needle complex is conserved among bacterial pathogens and shows broad similarity to the flagellar basal body. However, the TTSS of enteropathogenic and enterohemorrhagic Escherichia coli, two important human enteric pathogens, is unique in that it has a ~12-nmdiameter filamentous extension to the needle that is composed of the secreted translocator protein EspA. EspA filaments and flagellar structures have very similar helical symmetry parameters. In this study we investigated EspA filament assembly and the delivery of effector proteins across the bacterial cell wall. We show that EspA filaments are elongated by addition of EspA subunits to the tip of the growing filament. Moreover, EspA filament length is modulated by the availability of intracellular EspA subunits. Finally, we provide direct evidence that EspA filaments are hollow conduits through which effector proteins are delivered to the extremity of the bacterial cell (and subsequently into the host cell).

Published
2005

14. The Enterohemorrhagic Escherichia coli effector EspW triggers actin remodeling in a Rac1-dependent manner

Author

Sandu, Pamela, Crepin, Valerie F, Drechsler, Hauke, McAinsh, Andrew D, Frankel, Gad, and Berger, Cedric N

Subjects
bacteria, biochemical phenomena, metabolism, and nutrition, QR
Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a diarrheagenic pathogen that colonizes the gut mucosa and induces attaching-and-effacing lesions. EHEC employs a type III secretion system (T3SS) to translocate 50 effector proteins that hijack and manipulate host cell signaling pathways, which allow bacterial colonization and subversion of immune responses and disease progression. The aim of this study was to characterize the T3SS effector EspW. We found espW in the sequenced O157:H7 and non-O157 EHEC strains as well as in Shigella boydii. Furthermore, a truncated version of EspW, containing the first 206 residues, is present in EPEC strains belonging to serotype O55:H7. Screening a collection of clinical EPEC isolates revealed that espW is present in 52% of the tested strains. We report that EspW modulates actin dynamics in a Rac1-dependent manner. Ectopic expression of EspW results in formation of unique membrane protrusions. Infection of Swiss cells with an EHEC espW deletion mutant induces a cell shrinkage phenotype that could be rescued by Rac1 activation via expression of the bacterial guanine nucleotide exchange factor, EspT. Furthermore, using a yeast two-hybrid screen, we identified the motor protein Kif15 as a potential interacting partner of EspW. Kif15 and EspW colocalized in cotransfected cells, while ectopically expressed Kif15 localized to the actin pedestals following EHEC infection. The data suggest that Kif15 recruits EspW to the site of bacterial attachment, which in turn activates Rac1, resulting in modifications of the actin cytoskeleton that are essential to maintain cell shape during infection.

Published
2017

17. Author Correction: Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion

Author

Connolly, James P. R., primary, Slater, Sabrina L., additional, O’Boyle, Nicky, additional, Goldstone, Robert J., additional, Crepin, Valerie F., additional, Ruano-Gallego, David, additional, Herzyk, Pawel, additional, Smith, David G. E., additional, Douce, Gillian R., additional, Frankel, Gad, additional, and Roe, Andrew J., additional

Published
2018
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18. The Citrobacter rodentium type III secretion system effector EspO affects mucosal damage repair and antimicrobial responses

Author

Berger, Cedric N., primary, Crepin, Valerie F., additional, Roumeliotis, Theodoros I., additional, Wright, James C., additional, Serafini, Nicolas, additional, Pevsner-Fischer, Meirav, additional, Yu, Lu, additional, Elinav, Eran, additional, Di Santo, James P., additional, Choudhary, Jyoti S., additional, and Frankel, Gad, additional

Published
2018
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19. Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion

Author

Connolly, James P. R., primary, Slater, Sabrina L., additional, O’Boyle, Nicky, additional, Goldstone, Robert J., additional, Crepin, Valerie F., additional, Ruano-Gallego, David, additional, Herzyk, Pawel, additional, Smith, David G. E., additional, Douce, Gillian R., additional, Frankel, Gad, additional, and Roe, Andrew J., additional

Published
2018
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20. Citrobacter rodentium Relies on Commensals for Colonization of the Colonic Mucosa

Author

Mullineaux-Sanders, Caroline, primary, Collins, James W., additional, Ruano-Gallego, David, additional, Levy, Maayan, additional, Pevsner-Fischer, Meirav, additional, Glegola-Madejska, Izabela T., additional, Sågfors, Agnes M., additional, Wong, Joshua L.C., additional, Elinav, Eran, additional, Crepin, Valerie F., additional, and Frankel, Gad, additional

Published
2017
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21. The type III secretion system effector SptP of Salmonella enterica serovar Typhi

Author

Johnson, Rebecca, Byrne, Alexander, Berger, Cedric N, Klemm, Elizabeth, Crepin, Valerie F, Dougan, Gordon, Frankel, Gad, Medical Research Council (MRC), and Wellcome Trust

Subjects
bacteria, 11 Medical And Health Sciences, 07 Agricultural And Veterinary Sciences, 06 Biological Sciences, bacterial infections and mycoses, complex mixtures, Microbiology
Abstract

Strains of the various Salmonella enterica serovars cause gastroenteritis or typhoid fever in humans, with virulence depending on the action of two type III secretion systems (Salmonella pathogenicity island 1 [SPI-1] and SPI-2). SptP is a Salmonella SPI-1 effector, involved in mediating recovery of the host cytoskeleton postinfection. SptP requires a chaperone, SicP, for stability and secretion. SptP has 94% identity between S. enterica serovar Typhimurium and S. Typhi; direct comparison of the protein sequences revealed that S. Typhi SptP has numerous amino acid changes within its chaperone-binding domain. Subsequent comparison of ΔsptP S. Typhi and S. Typhimurium strains demonstrated that, unlike SptP in S. Typhimurium, SptP in S. Typhi was not involved in invasion or cytoskeletal recovery postinfection. Investigation of whether the observed amino acid changes within SptP of S. Typhi affected its function revealed that S. Typhi SptP was unable to complement S. Typhimurium ΔsptP due to an absence of secretion. We further demonstrated that while S. Typhimurium SptP is stable intracellularly within S. Typhi, S. Typhi SptP is unstable, although stability could be recovered following replacement of the chaperone-binding domain with that of S. Typhimurium. Direct assessment of the strength of the interaction between SptP and SicP of both serovars via bacterial two-hybrid analysis demonstrated that S. Typhi SptP has a significantly weaker interaction with SicP than the equivalent proteins in S. Typhimurium. Taken together, our results suggest that changes within the chaperone-binding domain of SptP in S. Typhi hinder binding to its chaperone, resulting in instability, preventing translocation, and therefore restricting the intracellular activity of this effector. IMPORTANCE Studies investigating Salmonella pathogenesis typically rely on Salmonella Typhimurium, even though Salmonella Typhi causes the more severe disease in humans. As such, an understanding of S. Typhi pathogenesis is lacking. Differences within the type III secretion system effector SptP between typhoidal and nontyphoidal serovars led us to characterize this effector within S. Typhi. Our results suggest that SptP is not translocated from typhoidal serovars, even though the loss of sptP results in virulence defects in S. Typhimurium. Although SptP is just one effector, our results exemplify that the behavior of these serovars is significantly different and genes identified to be important for S. Typhimurium virulence may not translate to S. Typhi.

Published
2016

22. Erratum: EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation

Author

Pearson, Jaclyn S., primary, Giogha, Cristina, additional, Mühlen, Sabrina, additional, Nachbur, Ueli, additional, Pham, Chi L. L., additional, Zhang, Ying, additional, Hildebrand, Joanne M., additional, Oates, Clare V., additional, Lung, Tania Wong Fok, additional, Ingle, Danielle, additional, Dagley, Laura F., additional, Bankovacki, Aleksandra, additional, Petrie, Emma J., additional, Schroeder, Gunnar N., additional, Crepin, Valerie F., additional, Frankel, Gad, additional, Masters, Seth L., additional, Vince, James, additional, Murphy, James M., additional, Sunde, Margaret, additional, Webb, Andrew I., additional, Silke, John, additional, and Hartland, Elizabeth L., additional

Published
2017
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23. EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation

Author

Pearson, Jaclyn S., primary, Giogha, Cristina, additional, Mühlen, Sabrina, additional, Nachbur, Ueli, additional, Pham, Chi L. L., additional, Zhang, Ying, additional, Hildebrand, Joanne M., additional, Oates, Clare V., additional, Lung, Tania Wong Fok, additional, Ingle, Danielle, additional, Dagley, Laura F., additional, Bankovacki, Aleksandra, additional, Petrie, Emma J., additional, Schroeder, Gunnar N., additional, Crepin, Valerie F., additional, Frankel, Gad, additional, Masters, Seth L., additional, Vince, James, additional, Murphy, James M., additional, Sunde, Margaret, additional, Webb, Andrew I., additional, Silke, John, additional, and Hartland, Elizabeth L., additional

Published
2017
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25. The enteropathogenic E. coli effector EspH promotes actin pedestal formation and elongation via WASP-interacting protein (WIP)

Author

Wong, Alexander R. C., Raymond, Benoit, Collins, James W., Crepin, Valerie F., and Frankel, Gad

Subjects
Escherichia coli Proteins, Intracellular Signaling Peptides and Proteins, macromolecular substances, biochemical phenomena, metabolism, and nutrition, digestive system, Models, Biological, Article, Actins, Endocytosis, Cytoskeletal Proteins, Enteropathogenic Escherichia coli, Protein Transport, parasitic diseases, bacteria, Bacterial Secretion Systems
Abstract

Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) are diarrheagenic pathogens that colonize the gut mucosa via attaching-and-effacing lesion formation. EPEC and EHEC utilize a type III secretion system (T3SS) to translocate effector proteins that subvert host cell signalling to sustain colonization and multiplication. EspH, a T3SS effector that modulates actin dynamics, was implicated in the elongation of the EHEC actin pedestals. In this study we found that EspH is necessary for both efficient pedestal formation and pedestal elongation during EPEC infection. We report that EspH induces actin polymerization at the bacterial attachment sites independently of the Tir tyrosine residues Y474 and Y454, which are implicated in binding Nck and IRSp53/ITRKS respectively. Moreover, EspH promotes recruitment of neural Wiskott-Aldrich syndrome protein (N-WASP) and the Arp2/3 complex to the bacterial attachment site, in a mechanism involving the C-terminus of Tir and the WH1 domain of N-WASP. Dominant negative of WASP-interacting protein (WIP), which binds the N-WASP WH1 domain, diminished EspH-mediated actin polymerization. This study implicates WIP in EPEC-mediated actin polymerization and pedestal elongation and represents the first instance whereby N-WASP is efficiently recruited to the EPEC attachment sites independently of the Tir:Nck and Tir:IRTKS/IRSp53 pathways. Our study reveals the intricacies of Tir and EspH-mediated actin signalling pathways that comprise of distinct, convergent and synergistic signalling cascades.

Published
2012

28. Citrobacter rodentiumRelies on Commensals for Colonization of the Colonic Mucosa

Author

Mullineaux-Sanders, Caroline, Collins, James W., Ruano-Gallego, David, Levy, Maayan, Pevsner-Fischer, Meirav, Glegola-Madejska, Izabela T., Sågfors, Agnes M., Wong, Joshua L.C., Elinav, Eran, Crepin, Valerie F., and Frankel, Gad

Abstract

We investigated the role of commensals at the peak of infection with the colonic mouse pathogen Citrobacter rodentium.Bioluminescent and kanamycin (Kan)-resistant C. rodentiumpersisted avirulently in the cecal lumen of mice continuously treated with Kan. A single Kan treatment was sufficient to displace C. rodentiumfrom the colonic mucosa, a phenomenon not observed following treatment with vancomycin (Van) or metronidazole (Met). Kan, Van, and Met induce distinct dysbiosis, suggesting C. rodentiumrelies on specific commensals for colonic colonization. Expression of the master virulence regulator leris induced in germ-free mice, yet C. rodentiumis only seen in the cecal lumen. Moreover, in conventional mice, a single Kan treatment was sufficient to displace C. rodentiumconstitutively expressing Ler from the colonic mucosa. These results show that expression of virulence genes is not sufficient for colonization of the colonic mucosa and that commensals are essential for a physiological infection course.

Published
2017
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33. Binding to Na+/H+ exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH

Author

Martinez, Eric, primary, Schroeder, Gunnar N., additional, Berger, Cedric N., additional, Lee, Sau Fung, additional, Robinson, Keith S., additional, Badea, Luminita, additional, Simpson, Nandi, additional, Hall, Randy A., additional, Hartland, Elizabeth L., additional, Crepin, Valerie F., additional, and Frankel, Gad, additional

Published
2010
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39. Role of NleH, a Type III Secreted Effector from Attaching and Effacing Pathogens, in Colonization of the Bovine, Ovine, and Murine Gut

Author

Hemrajani, Cordula, primary, Marches, Olivier, additional, Wiles, Siouxsie, additional, Girard, Francis, additional, Dennis, Alison, additional, Dziva, Francis, additional, Best, Angus, additional, Phillips, Alan D., additional, Berger, Cedric N., additional, Mousnier, Aurelie, additional, Crepin, Valerie F., additional, Kruidenier, Laurens, additional, Woodward, Martin J., additional, Stevens, Mark P., additional, La Ragione, Roberto M., additional, MacDonald, Thomas T., additional, and Frankel, Gad, additional

Published
2008
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48. The mechanisms used by enteropathogenic Escherichia coli to control filopodia dynamics.

Author

Berger, Cedric N., Crepin, Valerie F., Jepson, Mark A., Arbeloa, Ana, and Frankel, Gad

Subjects
*ESCHERICHIA coli, *EUKARYOTIC cells, *PROTEINS, *PHOSPHORYLATION, *INFECTION, *CELLS
Abstract

Enteropathogenic Escherichia coli (EPEC) subverts actin dynamics in eukaryotic cells by injecting effector proteins via a type III secretion system. First, WxxxE effector Map triggers transient formation of filopodia. Then, following recovery from the filopodial signals, EPEC triggers robust actin polymerization via a signalling complex comprising Tir and the adaptor proteins Nck. In this paper we show that Map triggers filopodia formation by activating Cdc42; expression of dominant-negative Cdc42 or knock-down of Cdc42 by siRNA impaired filopodia formation. In addition, Map binds PDZ1 of NHERF1. We show that Map–NHERF1 interaction is needed for filopodia stabilization in a process involving ezrin and the RhoA/ROCK cascade; expression of dominant-negative ezrin and RhoA or siRNA knock-down of RhoA lead to rapid elimination of filopodia. Moreover, we show that formation of the Tir-Nck signalling complex leads to filopodia withdrawal. Recovery from the filopodial signals requires phosphorylation of a Tir tyrosine (Y474) residue and actin polymerization pathway as both infection of cells with EPEC expressing TirY474S or infection of Nck knockout cells with wild-type EPEC resulted in persistence of filopodia. These results show that EPEC effectors modulate actin dynamics by temporal subverting the Rho GTPases and other actin polymerization pathways for the benefit of the adherent pathogen. [ABSTRACT FROM AUTHOR]

Published
2009
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49. The p50 Subunit of NF-κB Is Critical for In Vivo Clearance of the Noninvasive Enteric Pathogen Citrobacter rodentium

Author

Dennis, Alison, Kudo, Takahiro, Kruidenier, Laurens, Girard, Francis, Crepin, Valerie F., MacDonald, Thomas T., Frankel, Gad, and Wiles, Siouxsie

Abstract

ABSTRACTCitrobacter rodentium, a natural mouse pathogen, belongs to the family of extracellular enteric pathogens that includes enteropathogenic Escherichia coli(EPEC) and enterohemorrhagic E. coli(EHEC). C. rodentiumshares many virulence factors with EPEC and EHEC and relies on attaching-and-effacing lesion formation for colonization and infection of the gut. In vivo, C. rodentiuminfection is characterized by increased epithelial cell proliferation, mucosal thickening, and a TH1-type immune response, but with protective immunity believed to be mediated by serum immunoglobulin G (IgG). In this work, we characterize the immune response and pathology of mice lacking the p50 subunit of the transcription factor nuclear factor kappa B (NF-κB) during C. rodentiuminfection. We show that p50−/−mice are unable to clear C. rodentiuminfection. Furthermore, these animals show a reduced influx of immune cells into infected colonic tissue and greater levels of mucosal hyperplasia and the cytokines tumor necrosis factor alpha and gamma interferon. Surprisingly, despite being unable to eliminate infection, p50−/−mice showed markedly higher levels of anti-CitrobacterIgG and IgM, suggesting that antibody alone is not responsible for bacterial clearance. These data also demonstrate that non-NF-κB-dependent defenses are insufficient to control C. rodentiuminfection, and hence, the NF-κB p50 subunit is critical for defense against this noninvasive pathogen.

Published
2008
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50. The p50 Subunit of NF-B Is Critical for In Vivo Clearance of the Noninvasive Enteric Pathogen Citrobacter rodentium

Author

Dennis, Alison, Kudo, Takahiro, Kruidenier, Laurens, Girard, Francis, Crepin, Valerie F., MacDonald, Thomas T., Frankel, Gad, and Wiles, Siouxsie

Abstract

Citrobacter rodentium, a natural mouse pathogen, belongs to the family of extracellular enteric pathogens that includes enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). C. rodentium shares many virulence factors with EPEC and EHEC and relies on attaching-and-effacing lesion formation for colonization and infection of the gut. In vivo, C. rodentium infection is characterized by increased epithelial cell proliferation, mucosal thickening, and a TH1-type immune response, but with protective immunity believed to be mediated by serum immunoglobulin G (IgG). In this work, we characterize the immune response and pathology of mice lacking the p50 subunit of the transcription factor nuclear factor kappa B (NF-B) during C. rodentium infection. We show that p50–/–mice are unable to clear C. rodentium infection. Furthermore, these animals show a reduced influx of immune cells into infected colonic tissue and greater levels of mucosal hyperplasia and the cytokines tumor necrosis factor alpha and gamma interferon. Surprisingly, despite being unable to eliminate infection, p50–/–mice showed markedly higher levels of anti-Citrobacter IgG and IgM, suggesting that antibody alone is not responsible for bacterial clearance. These data also demonstrate that non-NF-B-dependent defenses are insufficient to control C. rodentium infection, and hence, the NF-B p50 subunit is critical for defense against this noninvasive pathogen.

Published
2008

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