Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naÃ¯ve T-cells but no enduring cell-autonomous defects in T-cell function

Robby Markwart; Stephanie A Condotta; Robert P Requardt; Farina Borken; Katja Schubert; Cynthia Weigel; Michael Bauer; Thomas S Griffith; Martin Förster; Frank M Brunkhorst; Vladimir P Badovinac; Ignacio Rubio

doi:10.1371/journal.pone.0115094

Back

Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naÃ¯ve T-cells but no enduring cell-autonomous defects in T-cell function

Journal article

Open access

Peer reviewed

Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naÃ¯ve T-cells but no enduring cell-autonomous defects in T-cell function

Robby Markwart, Stephanie A Condotta, Robert P Requardt, Farina Borken, Katja Schubert, Cynthia Weigel, Michael Bauer, Thomas S Griffith, Martin Förster, Frank M Brunkhorst, …

PloS one, Vol.9(12), pp.e115094-e115094

2014

DOI: 10.1371/journal.pone.0115094

PMCID: PMC4277344

PMID: 25541945

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0115094View

Published (Version of record) Open Access

Abstract

Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4(+)/CD8(+) T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells.

Adaptive Immunity

Sepsis - immunology

Cytokines - metabolism

Receptors, Antigen, T-Cell - metabolism

Humans

Mice, Inbred C57BL

Mice, Transgenic

Sepsis - complications

Inflammation - immunology

Animals

Immunosuppression - adverse effects

T-Lymphocytes - cytology

T-Lymphocytes - immunology

Lymphopenia - immunology

Mice

Disease Models, Animal

Details

Title: Subtitle: Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naÃ¯ve T-cells but no enduring cell-autonomous defects in T-cell function
Creators: Robby Markwart - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
Stephanie A Condotta - Dept. of Pathology, University of Iowa, Iowa City, Iowa, United States of America
Robert P Requardt - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
Farina Borken - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
Katja Schubert - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
Cynthia Weigel - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany
Michael Bauer - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Dept. for Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
Thomas S Griffith - Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota, United States of America; Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America
Martin Förster - Clinic of Internal Medicine I, Jena University Hospital, Jena, Germany
Frank M Brunkhorst - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Center for Clinical Studies, Jena University Hospital, Jena, Germany
Vladimir P Badovinac - Dept. of Pathology, University of Iowa, Iowa City, Iowa, United States of America
Ignacio Rubio - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Jena, Germany
Resource Type: Journal article
Publication Details: PloS one, Vol.9(12), pp.e115094-e115094
DOI: 10.1371/journal.pone.0115094
PMID: 25541945
PMCID: PMC4277344
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: AI83286 / NIAID NIH HHS I01 BX001324 / BLRD VA R01 AI114543 / NIAID NIH HHS AI114543 / NIAID NIH HHS R01 AI083286 / NIAID NIH HHS
Language: English
Date published: 2014
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984046920102771

Metrics

8 Record Views

56 Times Cited - Web of Science