Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis

Tali Lang, Christoph Hudemann, Svetlin Tchatalbachev, Angelika Stammler, Vera Michel, Ferial Aslani, Sudhanshu Bhushan, Trinad Chakraborty, Harald Renz, Andreas Meinhardt

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Infectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis is Escherichia coli. In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specific E. coli pathovars. Thus, our aim was to investigate possible differences in immune responses elicited during epididymitis following infection with the uropathogenic E. coli (UPEC) strain CFT073 and the nonpathogenic enteric E. coli (NPEC) strain 470. Employing an in vivo experimental epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or phosphate-buffered saline (PBS) as a sham control for up to 7 days. After infection with NPEC 470, the expression of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3+ and F4/80+ cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated cytokines IL-2 and gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of epididymitis, which may influence severity of disease and clinical outcomes.

Original languageEnglish
Pages (from-to)1104-1111
Number of pages8
JournalInfection and Immunity
Volume82
Issue number3
DOIs
Publication statusPublished - Mar 2014
Externally publishedYes

Cite this

Lang, Tali ; Hudemann, Christoph ; Tchatalbachev, Svetlin ; Stammler, Angelika ; Michel, Vera ; Aslani, Ferial ; Bhushan, Sudhanshu ; Chakraborty, Trinad ; Renz, Harald ; Meinhardt, Andreas. / Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis. In: Infection and Immunity. 2014 ; Vol. 82, No. 3. pp. 1104-1111.
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title = "Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis",
abstract = "Infectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis is Escherichia coli. In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specific E. coli pathovars. Thus, our aim was to investigate possible differences in immune responses elicited during epididymitis following infection with the uropathogenic E. coli (UPEC) strain CFT073 and the nonpathogenic enteric E. coli (NPEC) strain 470. Employing an in vivo experimental epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or phosphate-buffered saline (PBS) as a sham control for up to 7 days. After infection with NPEC 470, the expression of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3+ and F4/80+ cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated cytokines IL-2 and gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of epididymitis, which may influence severity of disease and clinical outcomes.",
author = "Tali Lang and Christoph Hudemann and Svetlin Tchatalbachev and Angelika Stammler and Vera Michel and Ferial Aslani and Sudhanshu Bhushan and Trinad Chakraborty and Harald Renz and Andreas Meinhardt",
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Lang, T, Hudemann, C, Tchatalbachev, S, Stammler, A, Michel, V, Aslani, F, Bhushan, S, Chakraborty, T, Renz, H & Meinhardt, A 2014, 'Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis', Infection and Immunity, vol. 82, no. 3, pp. 1104-1111. https://doi.org/10.1128/IAI.01373-13

Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis. / Lang, Tali; Hudemann, Christoph; Tchatalbachev, Svetlin; Stammler, Angelika; Michel, Vera; Aslani, Ferial; Bhushan, Sudhanshu; Chakraborty, Trinad; Renz, Harald; Meinhardt, Andreas.

In: Infection and Immunity, Vol. 82, No. 3, 03.2014, p. 1104-1111.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis

AU - Lang, Tali

AU - Hudemann, Christoph

AU - Tchatalbachev, Svetlin

AU - Stammler, Angelika

AU - Michel, Vera

AU - Aslani, Ferial

AU - Bhushan, Sudhanshu

AU - Chakraborty, Trinad

AU - Renz, Harald

AU - Meinhardt, Andreas

PY - 2014/3

Y1 - 2014/3

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AB - Infectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis is Escherichia coli. In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specific E. coli pathovars. Thus, our aim was to investigate possible differences in immune responses elicited during epididymitis following infection with the uropathogenic E. coli (UPEC) strain CFT073 and the nonpathogenic enteric E. coli (NPEC) strain 470. Employing an in vivo experimental epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or phosphate-buffered saline (PBS) as a sham control for up to 7 days. After infection with NPEC 470, the expression of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3+ and F4/80+ cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated cytokines IL-2 and gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of epididymitis, which may influence severity of disease and clinical outcomes.

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