@article{2553d14e9b584834b1ed3ff69226c566,
title = "Mucosal infection rewires TNFα signaling dynamics to skew susceptibility to recurrence",
abstract = "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 (TNFa)- mediated bladder inflammation upon subsequent bacterial challenge, relative to age-matched naive mice. However, the duration of TNFa signaling activation differed according to whether the first infection was chronic (Sensitized) or self-limiting (Resolved). TNFa depletion studies revealed that transient early-phase TNFa 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 TNFa signaling in Sensitized mice prolonged damaging inflammation, worsening infection. This work reveals how TNFa signaling dynamics can be rewired by a prior infection to shape diverse susceptibilities to future mucosal infections.",
author = "Lu Yu and O{\textquoteright}Brien, {Valerie P.} and Jonathan Livny and Denise Dorsey and Nirmalya Bandyopadhyay and Marco Colonna and Caparon, {Michael G.} and Roberson, {Elisha D.O.} and Hultgren, {Scott J.} and Hannan, {Thomas J.}",
note = "Funding Information: The authors thank Danielle Liu for technical assistance and Karen Dodson for editorial assistance. This work was supported by the National Institutes of Health (R01 DK51406 to SJH, U01 AI95542 to MC, SJH and TJH, K08 AI083746 to TJH); the Office of Research on Women{\textquoteright}s Health Specialized Center of Research (P50 DK64540), URL: https://orwh.od.nih.gov; a National Institutes of Health Mucosal Immunology Studies Team consortium Young Investigator Award (U01 AI095776 to TJH), URL: https://www.mucosal.org; and the National Science Foundation (Graduate Research Fellowship #DGE–114395 to VPO), URL: https://www.nsfgrfp.org/. As well, scanning electron microscopy sample preparation and imaging was conducted at the Washington University Center for Cellular Imaging (WUCCI), which is supported by the Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015–505), and the Foundation for Barnes-Jewish Hospital (3770). RNA-seq analysis design and support was provided by the Rheumatic Diseases Research Resource-based Center at Washington University (EDOR was partially supported by NIH/NIAMS grant P30-AR073752) and The Broad Institute of Massachusetts Institute of Technology and Harvard (JL has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Grant Number U19AI110818 to the Broad Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: National Institute of Diabetes and Digestive and Kidney Diseases R01 DK51406 Scott Hultgren National Institute of Allergy and Infectious Diseases U01 AI95542 Marco Colonna Scott Hultgren Thomas J. Hannan National Institute of Allergy and Infectious Diseases K08 AI083746 Thomas J. Hannan NIH Office of the Director P50 DK64540 Scott Hultgren National Institute of Allergy and Infectious Diseases U01 AI095776 Thomas J. Hannan National Science Foundation Graduate Research Fellowship #DGE-114395 Valerie Phoebe O'Brien National Institute of Arthritis and Musculoskeletal and Skin Diseases P30 AR073752 Elisha D.O. Roberson National Institute of Allergy and Infectious Diseases U19 AI110818 Jonathan Livny Publisher Copyright: {\textcopyright} Yu et al.",
year = "2019",
month = aug,
doi = "10.7554/eLife.46677",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
}