S100A9 is indispensable for survival of pneumococcal pneumonia in mice
Copyright: © 2023 Ostermann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn2+ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
PLoS pathogens - 19(2023), 7 vom: 26. Juli, Seite e1011493 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ostermann, Lena [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Calgranulin A |
|---|
| Anmerkungen: |
Date Completed 21.07.2023 Date Revised 21.07.2023 published: Electronic-eCollection DRKS: DRKS00000620 Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.ppat.1011493 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359676979 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359676979 | ||
| 003 | DE-627 | ||
| 005 | 20231226081402.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.ppat.1011493 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1198.xml |
| 035 | |a (DE-627)NLM359676979 | ||
| 035 | |a (NLM)37467233 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ostermann, Lena |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a S100A9 is indispensable for survival of pneumococcal pneumonia in mice |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.07.2023 | ||
| 500 | |a Date Revised 21.07.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a DRKS: DRKS00000620 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2023 Ostermann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn2+ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Calgranulin B |2 NLM | |
| 650 | 7 | |a Calgranulin A |2 NLM | |
| 650 | 7 | |a S100A9 protein, mouse |2 NLM | |
| 700 | 1 | |a Seeliger, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a David, Sascha |e verfasserin |4 aut | |
| 700 | 1 | |a Flasche, Carolin |e verfasserin |4 aut | |
| 700 | 1 | |a Maus, Regina |e verfasserin |4 aut | |
| 700 | 1 | |a Reinboth, Marieke S |e verfasserin |4 aut | |
| 700 | 1 | |a Christmann, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Neumann, Konstantin |e verfasserin |4 aut | |
| 700 | 1 | |a Brand, Korbinian |e verfasserin |4 aut | |
| 700 | 1 | |a Seltmann, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Bühling, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Paton, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Roth, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Vogl, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Viemann, Dorothee |e verfasserin |4 aut | |
| 700 | 1 | |a Welte, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Maus, Ulrich A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PLoS pathogens |d 2005 |g 19(2023), 7 vom: 26. Juli, Seite e1011493 |w (DE-627)NLM158124782 |x 1553-7374 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2023 |g number:7 |g day:26 |g month:07 |g pages:e1011493 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.ppat.1011493 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2023 |e 7 |b 26 |c 07 |h e1011493 | ||