Suppression of NF-kappaB-mediated Beta-defensin Gene Expression in the Mammalian Airway by the Bordetella Type III Secretion System

Overview

Journal Cell Microbiol

Publisher Wiley

Specialties Cell Biology
Microbiology

Date 2005 Mar 12

PMID 15760449

Citations 19

Authors

Diana Legarda

Marcia E Klein-Patel

Sunghan Yim

Ming H Yuk

Gill Diamond

Affiliations

Soon will be listed here.

Abstract

Expression of innate immune genes such as beta-defensins is induced in airway epithelium by bacterial components via activation of NF-kappaB. We show here that live Gram-negative bacteria can similarly stimulate this pathway, resulting in upregulation of the beta-defensin tracheal antimicrobial peptide (TAP) in primary cultures of bovine tracheal epithelial cells (TECs), by a Toll-like receptor 4 (TLR4)-mediated pathway. The Gram-negative airway pathogen Bordetella bronchiseptica possesses a type III secretion system previously suggested to inhibit the nuclear translocation of NF-kappaB in a cell line by immunohistochemistry. We therefore hypothesized that this pathogen might interfere in the innate immune response of the epithelium. Exposure of TECs to wild-type B. bronchiseptica suppressed the activation of NF-kappaB and the subsequent induction of TAP mRNA levels, whereas a type III secretion-defective strain did not. These results suggest a mechanism for bacterial evasion of the innate immune response in the airway, which could allow for the observed persistent colonization of this pathogen.

Citing Articles

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Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue.

Bayram J, Malcova I, Sinkovec L, Holubova J, Streparola G, Jurnecka D PLoS Pathog. 2020; 16(8):e1008512.

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β-Defensins Coordinate In Vivo to Inhibit Bacterial Infections of the Trachea.

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Rediscovering Pertussis.

Zlamy M Front Pediatr. 2016; 4:52.

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Differential regulation of type III secretion and virulence genes in Bordetella pertussis and Bordetella bronchiseptica by a secreted anti-σ factor.

Ahuja U, Shokeen B, Cheng N, Cho Y, Blum C, Coppola G Proc Natl Acad Sci U S A. 2016; 113(9):2341-8.

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References

ONeil D, Porter E, Elewaut D, Anderson G, Eckmann L, Ganz T . Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol. 1999; 163(12):6718-24. View

Diamond G, Zasloff M, ECK H, Brasseur M, Maloy W, Bevins C . Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A. 1991; 88(9):3952-6. PMC: 51571. DOI: 10.1073/pnas.88.9.3952. View

Diamond G, Jones D, Bevins C . Airway epithelial cells are the site of expression of a mammalian antimicrobial peptide gene. Proc Natl Acad Sci U S A. 1993; 90(10):4596-600. PMC: 46559. DOI: 10.1073/pnas.90.10.4596. View

Cotter P, Miller J . BvgAS-mediated signal transduction: analysis of phase-locked regulatory mutants of Bordetella bronchiseptica in a rabbit model. Infect Immun. 1994; 62(8):3381-90. PMC: 302969. DOI: 10.1128/iai.62.8.3381-3390.1994. View

Beuscher H, Rodel F, Forsberg A, Rollinghoff M . Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression. Infect Immun. 1995; 63(4):1270-7. PMC: 173146. DOI: 10.1128/iai.63.4.1270-1277.1995. View

Russell J, Diamond G, Tarver A, Scanlin T, Bevins C . Coordinate induction of two antibiotic genes in tracheal epithelial cells exposed to the inflammatory mediators lipopolysaccharide and tumor necrosis factor alpha. Infect Immun. 1996; 64(5):1565-8. PMC: 173962. DOI: 10.1128/iai.64.5.1565-1568.1996. View

Diamond G, Russell J, Bevins C . Inducible expression of an antibiotic peptide gene in lipopolysaccharide-challenged tracheal epithelial cells. Proc Natl Acad Sci U S A. 1996; 93(10):5156-60. PMC: 39424. DOI: 10.1073/pnas.93.10.5156. View

Martinez de Tejada G, Miller J, Cotter P . Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica. Mol Microbiol. 1996; 22(5):895-908. DOI: 10.1046/j.1365-2958.1996.01538.x. View

Ruckdeschel K, Machold J, Roggenkamp A, Schubert S, Pierre J, Zumbihl R . Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha.... J Biol Chem. 1997; 272(25):15920-7. DOI: 10.1074/jbc.272.25.15920. View

10.

Cotter P, Miller J . A mutation in the Bordetella bronchiseptica bvgS gene results in reduced virulence and increased resistance to starvation, and identifies a new class of Bvg-regulated antigens. Mol Microbiol. 1997; 24(4):671-85. DOI: 10.1046/j.1365-2958.1997.3821741.x. View

11.

Ryan L, Rhodes J, Bhat M, Diamond G . Expression of beta-defensin genes in bovine alveolar macrophages. Infect Immun. 1998; 66(2):878-81. PMC: 107989. DOI: 10.1128/IAI.66.2.878-881.1998. View

12.

Boland A, Cornelis G . Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during Yersinia infection. Infect Immun. 1998; 66(5):1878-84. PMC: 108138. DOI: 10.1128/IAI.66.5.1878-1884.1998. View

13.

Li J, Feng W, Gallup M, Kim J, Gum J, Kim Y . Activation of NF-kappaB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells. Proc Natl Acad Sci U S A. 1998; 95(10):5718-23. PMC: 20445. DOI: 10.1073/pnas.95.10.5718. View

14.

Yuk M, Harvill E, Miller J . The BvgAS virulence control system regulates type III secretion in Bordetella bronchiseptica. Mol Microbiol. 1998; 28(5):945-59. DOI: 10.1046/j.1365-2958.1998.00850.x. View

15.

Schesser K, Spiik A, Dukuzumuremyi J, Neurath M, Pettersson S, Wolf-Watz H . The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol Microbiol. 1998; 28(6):1067-79. DOI: 10.1046/j.1365-2958.1998.00851.x. View

16.

Diamond G, Bevins C . beta-Defensins: endogenous antibiotics of the innate host defense response. Clin Immunol Immunopathol. 1998; 88(3):221-5. DOI: 10.1006/clin.1998.4587. View

17.

Palmer L, Pancetti A, Greenberg S, Bliska J . YopJ of Yersinia spp. is sufficient to cause downregulation of multiple mitogen-activated protein kinases in eukaryotic cells. Infect Immun. 1999; 67(2):708-16. PMC: 96377. DOI: 10.1128/IAI.67.2.708-716.1999. View

18.

Galan J, Collmer A . Type III secretion machines: bacterial devices for protein delivery into host cells. Science. 1999; 284(5418):1322-8. DOI: 10.1126/science.284.5418.1322. View

19.

Orth K, Palmer L, Bao Z, Stewart S, Rudolph A, Bliska J . Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science. 1999; 285(5435):1920-3. DOI: 10.1126/science.285.5435.1920. View

20.

Diamond G, Legarda D, Ryan L . The innate immune response of the respiratory epithelium. Immunol Rev. 2000; 173:27-38. DOI: 10.1034/j.1600-065x.2000.917304.x. View