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Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence

A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infecti...

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Autores principales: Yu, Lu, O'Brien, Valerie P, Livny, Jonathan, Dorsey, Denise, Bandyopadhyay, Nirmalya, Colonna, Marco, Caparon, Michael G, Roberson, Elisha DO, Hultgren, Scott J, Hannan, Thomas J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701943/
https://www.ncbi.nlm.nih.gov/pubmed/31429405
http://dx.doi.org/10.7554/eLife.46677
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author Yu, Lu
O'Brien, Valerie P
Livny, Jonathan
Dorsey, Denise
Bandyopadhyay, Nirmalya
Colonna, Marco
Caparon, Michael G
Roberson, Elisha DO
Hultgren, Scott J
Hannan, Thomas J
author_facet Yu, Lu
O'Brien, Valerie P
Livny, Jonathan
Dorsey, Denise
Bandyopadhyay, Nirmalya
Colonna, Marco
Caparon, Michael G
Roberson, Elisha DO
Hultgren, Scott J
Hannan, Thomas J
author_sort Yu, Lu
collection PubMed
description A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice promoted clearance of bladder-colonizing bacteria via rapid recruitment of neutrophils and subsequent exfoliation of infected bladder cells. In contrast, sustained TNFɑ signaling in Sensitized mice prolonged damaging inflammation, worsening infection. This work reveals how TNFɑ signaling dynamics can be rewired by a prior infection to shape diverse susceptibilities to future mucosal infections.
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spelling pubmed-67019432019-08-22 Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence Yu, Lu O'Brien, Valerie P Livny, Jonathan Dorsey, Denise Bandyopadhyay, Nirmalya Colonna, Marco Caparon, Michael G Roberson, Elisha DO Hultgren, Scott J Hannan, Thomas J eLife Immunology and Inflammation A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but the specific mechanisms that tip the balance remain unclear. We investigated this question in a mouse model of recurrent urinary tract infection and found that a prior bladder infection resulted in an earlier onset of tumor necrosis factor-alpha (TNFɑ)-mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFɑ signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFɑ depletion studies revealed that transient early-phase TNFɑ signaling in Resolved mice promoted clearance of bladder-colonizing bacteria via rapid recruitment of neutrophils and subsequent exfoliation of infected bladder cells. In contrast, sustained TNFɑ signaling in Sensitized mice prolonged damaging inflammation, worsening infection. This work reveals how TNFɑ signaling dynamics can be rewired by a prior infection to shape diverse susceptibilities to future mucosal infections. eLife Sciences Publications, Ltd 2019-08-20 /pmc/articles/PMC6701943/ /pubmed/31429405 http://dx.doi.org/10.7554/eLife.46677 Text en © 2019, Yu et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Yu, Lu
O'Brien, Valerie P
Livny, Jonathan
Dorsey, Denise
Bandyopadhyay, Nirmalya
Colonna, Marco
Caparon, Michael G
Roberson, Elisha DO
Hultgren, Scott J
Hannan, Thomas J
Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
title Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
title_full Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
title_fullStr Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
title_full_unstemmed Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
title_short Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence
title_sort mucosal infection rewires tnfɑ signaling dynamics to skew susceptibility to recurrence
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701943/
https://www.ncbi.nlm.nih.gov/pubmed/31429405
http://dx.doi.org/10.7554/eLife.46677
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