Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783445139114426368 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6701943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yulu mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT obrienvaleriep mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT livnyjonathan mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT dorseydenise mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT bandyopadhyaynirmalya mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT colonnamarco mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT caparonmichaelg mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT robersonelishado mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT hultgrenscottj mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence AT hannanthomasj mucosalinfectionrewirestnfɑsignalingdynamicstoskewsusceptibilitytorecurrence |