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Title: Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology

Abstract

Immune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long-term control of infection while also preventing an over-zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro- and anti-inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying the signals, cells, cytokines, and other immune response factors that mediate this balance over time has been difficult using traditional research strategies. Computational modeling studies based on data from traditional systems can identify how this balance contributes to immunity. Here we provide evidence from both experimental and mathematical/computational studies to support the concept of a dynamic balance operating during persistent and other infection scenarios. We focus mainly on tuberculosis, currently the leading cause of death due to infectious disease in the world, and also provide evidence for other infections. A better understanding of the dynamically balanced immune response can help shape treatment strategies that utilize both drugs and host-directed therapies.

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1]; ORCiD logo [4]; ORCiD logo [1]; ORCiD logo [2]
  1. Univ. of Michigan, Ann Arbor, MI (United States)
  2. Univ. of Michigan Medical School, Ann Arbor, MI (United States)
  3. Univ. of Michigan, Ann Arbor, MI (United States); Univ. of Michigan Medical School, Ann Arbor, MI (United States)
  4. Univ. of Pittsburgh, PA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1543993
Alternate Identifier(s):
OSTI ID: 1471137
Resource Type:
Accepted Manuscript
Journal Name:
Immunological Reviews
Additional Journal Information:
Journal Volume: 285; Journal Issue: 1; Journal ID: ISSN 0105-2896
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Immunology

Citation Formats

Cicchese, Joseph M., Evans, Stephanie, Hult, Caitlin, Joslyn, Louis R., Wessler, Timothy, Millar, Jess A., Marino, Simeone, Cilfone, Nicholas A., Mattila, Joshua T., Linderman, Jennifer J., and Kirschner, Denise E. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. United States: N. p., 2018. Web. doi:10.1111/imr.12671.
Cicchese, Joseph M., Evans, Stephanie, Hult, Caitlin, Joslyn, Louis R., Wessler, Timothy, Millar, Jess A., Marino, Simeone, Cilfone, Nicholas A., Mattila, Joshua T., Linderman, Jennifer J., & Kirschner, Denise E. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. United States. doi:10.1111/imr.12671.
Cicchese, Joseph M., Evans, Stephanie, Hult, Caitlin, Joslyn, Louis R., Wessler, Timothy, Millar, Jess A., Marino, Simeone, Cilfone, Nicholas A., Mattila, Joshua T., Linderman, Jennifer J., and Kirschner, Denise E. Sat . "Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology". United States. doi:10.1111/imr.12671. https://www.osti.gov/servlets/purl/1543993.
@article{osti_1543993,
title = {Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology},
author = {Cicchese, Joseph M. and Evans, Stephanie and Hult, Caitlin and Joslyn, Louis R. and Wessler, Timothy and Millar, Jess A. and Marino, Simeone and Cilfone, Nicholas A. and Mattila, Joshua T. and Linderman, Jennifer J. and Kirschner, Denise E.},
abstractNote = {Immune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long-term control of infection while also preventing an over-zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro- and anti-inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying the signals, cells, cytokines, and other immune response factors that mediate this balance over time has been difficult using traditional research strategies. Computational modeling studies based on data from traditional systems can identify how this balance contributes to immunity. Here we provide evidence from both experimental and mathematical/computational studies to support the concept of a dynamic balance operating during persistent and other infection scenarios. We focus mainly on tuberculosis, currently the leading cause of death due to infectious disease in the world, and also provide evidence for other infections. A better understanding of the dynamically balanced immune response can help shape treatment strategies that utilize both drugs and host-directed therapies.},
doi = {10.1111/imr.12671},
journal = {Immunological Reviews},
number = 1,
volume = 285,
place = {United States},
year = {2018},
month = {8}
}

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