Journal article

Publication year: 2003

Pages: 2074-2082

Journal: The Journal of Immunology

Volume number: 170

Issue number: 4

ISSN: 0022-1767

DOI Link: https://doi.org/10.4049/jimmunol.170.4.2074

Publisher: American Association of Immunologists

Abstract: 
The NF-kappaB family of transcription factors forms one of the first lines of defense against infectious disease by inducing the expression of genes involved in inflammatory and immune responses. In this study, we analyzed the impact of Shiga toxin-producing Escherichia coli (STEC) on the NF-kappaB DNA-binding activity in HeLa cells. After a period of weak initial activation, DNA binding of NF-kappaB was actively suppressed by viable, E. coli secreted protein B (EspB)-secreting STEC. Sustained NF-kappaB activity was observed either using an isogenic mutant lacking EspB or after gentamicin-based killing of STEC after allowing bacterial attachment. These observations indicate that the ability of STEC to cause NF-kappaB activation is suppressed by a translocated bacterial effector protein, which is either EspB itself or requires EspB for delivery into the host cell. We found that STEC, enterohemorrhagic E. coli, and enteropathogenic E. coli all interfere with NF-kappaB activation initiated by TNF-alpha, indicating that suppression of signal-induced NF-kappaB activity is a property common to several attaching and effacing bacteria. As a consequence of NF-kappaB suppression, wild-type STEC induces significantly lower mRNA levels of IL-8, IL-6, and IL-1alpha upon prolonged infection periods compared with bacteria lacking EspB. For IL-8 and IL-6, the suppressive effect was also reflected at the level of cytokine secretion. Suppression of both basal and signal-induced NF-kappaB DNA binding by attaching and effacing-inducing bacteria appears to be an active strategy to counteract host defense responses, thus favoring intestinal colonization by these pathogens.

Harvard Citation style: Hauf, N. and Chakraborty, T. (2003) Suppression of NF-κB activation and proinflammatory cytokine expression by Shiga toxin-producing Escherichia coli, The Journal of Immunology, 170(4), pp. 2074-2082. https://doi.org/10.4049/jimmunol.170.4.2074

APA Citation style: Hauf, N., & Chakraborty, T. (2003). Suppression of NF-κB activation and proinflammatory cytokine expression by Shiga toxin-producing Escherichia coli. The Journal of Immunology. 170(4), 2074-2082. https://doi.org/10.4049/jimmunol.170.4.2074