Cargando…

Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin)...

Descripción completa

Detalles Bibliográficos
Autores principales: Shankar, Madhu, Uwamahoro, Nathalie, Backman, Emelie, Holmberg, Sandra, Niemiec, Maria Joanna, Roth, Johannes, Vogl, Thomas, Urban, Constantin F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953150/
https://www.ncbi.nlm.nih.gov/pubmed/33717058
http://dx.doi.org/10.3389/fimmu.2021.553911
_version_ 1783663863969873920
author Shankar, Madhu
Uwamahoro, Nathalie
Backman, Emelie
Holmberg, Sandra
Niemiec, Maria Joanna
Roth, Johannes
Vogl, Thomas
Urban, Constantin F.
author_facet Shankar, Madhu
Uwamahoro, Nathalie
Backman, Emelie
Holmberg, Sandra
Niemiec, Maria Joanna
Roth, Johannes
Vogl, Thomas
Urban, Constantin F.
author_sort Shankar, Madhu
collection PubMed
description Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.
format Online
Article
Text
id pubmed-7953150
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79531502021-03-13 Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis Shankar, Madhu Uwamahoro, Nathalie Backman, Emelie Holmberg, Sandra Niemiec, Maria Joanna Roth, Johannes Vogl, Thomas Urban, Constantin F. Front Immunol Immunology Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease. Frontiers Media S.A. 2021-02-26 /pmc/articles/PMC7953150/ /pubmed/33717058 http://dx.doi.org/10.3389/fimmu.2021.553911 Text en Copyright © 2021 Shankar, Uwamahoro, Backman, Holmberg, Niemiec, Roth, Vogl and Urban http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Shankar, Madhu
Uwamahoro, Nathalie
Backman, Emelie
Holmberg, Sandra
Niemiec, Maria Joanna
Roth, Johannes
Vogl, Thomas
Urban, Constantin F.
Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
title Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
title_full Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
title_fullStr Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
title_full_unstemmed Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
title_short Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
title_sort immune resolution dilemma: host antimicrobial factor s100a8/a9 modulates inflammatory collateral tissue damage during disseminated fungal peritonitis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953150/
https://www.ncbi.nlm.nih.gov/pubmed/33717058
http://dx.doi.org/10.3389/fimmu.2021.553911
work_keys_str_mv AT shankarmadhu immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT uwamahoronathalie immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT backmanemelie immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT holmbergsandra immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT niemiecmariajoanna immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT rothjohannes immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT voglthomas immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis
AT urbanconstantinf immuneresolutiondilemmahostantimicrobialfactors100a8a9modulatesinflammatorycollateraltissuedamageduringdisseminatedfungalperitonitis