Cellular and molecular dynamics in the lungs of neonatal and juvenile mice in response to E. coli
© 2023, McGrath-Morrow et al..
Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that underlie these age-related differences, we employed a mouse model of Escherichia coli pneumonia to determine the dynamic cellular and molecular differences in immune responsiveness between neonates (PND 3-5) and juveniles (PND 12-18), at 24, 48, and 72 hr. Cytokine gene expression from whole lung extracts was also quantified at these time points, using quantitative RT-PCR. E. coli challenge resulted in rapid and significant increases in neutrophils, monocytes, and γδT cells, along with significant decreases in dendritic cells and alveolar macrophages in the lungs of both neonates and juveniles. E. coli-challenged juvenile lung had significant increases in interstitial macrophages and recruited monocytes that were not observed in neonatal lungs. Expression of IFNγ-responsive genes was positively correlated with the levels and dynamics of MHCII-expressing innate cells in neonatal and juvenile lungs. Several facets of immune responsiveness in the wild-type neonates were recapitulated in juvenile MHCII-/- juveniles. Employing a pre-clinical model of E. coli pneumonia, we identified significant differences in the early cellular and molecular dynamics in the lungs that likely contribute to the elevated susceptibility of neonates to bacterial pneumonia and could represent targets for intervention to improve respiratory outcomes and survivability of neonates.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
eLife - 12(2023) vom: 02. Juni |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
McGrath-Morrow, Sharon A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Cytokines |
|---|
| Anmerkungen: |
Date Completed 15.06.2023 Date Revised 21.12.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.7554/eLife.82933 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM357686063 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM357686063 | ||
| 003 | DE-627 | ||
| 005 | 20231227135220.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.7554/eLife.82933 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1234.xml |
| 035 | |a (DE-627)NLM357686063 | ||
| 035 | |a (NLM)37266566 | ||
| 035 | |a (PII)e82933 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a McGrath-Morrow, Sharon A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cellular and molecular dynamics in the lungs of neonatal and juvenile mice in response to E. coli |
| 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 15.06.2023 | ||
| 500 | |a Date Revised 21.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023, McGrath-Morrow et al. | ||
| 520 | |a Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that underlie these age-related differences, we employed a mouse model of Escherichia coli pneumonia to determine the dynamic cellular and molecular differences in immune responsiveness between neonates (PND 3-5) and juveniles (PND 12-18), at 24, 48, and 72 hr. Cytokine gene expression from whole lung extracts was also quantified at these time points, using quantitative RT-PCR. E. coli challenge resulted in rapid and significant increases in neutrophils, monocytes, and γδT cells, along with significant decreases in dendritic cells and alveolar macrophages in the lungs of both neonates and juveniles. E. coli-challenged juvenile lung had significant increases in interstitial macrophages and recruited monocytes that were not observed in neonatal lungs. Expression of IFNγ-responsive genes was positively correlated with the levels and dynamics of MHCII-expressing innate cells in neonatal and juvenile lungs. Several facets of immune responsiveness in the wild-type neonates were recapitulated in juvenile MHCII-/- juveniles. Employing a pre-clinical model of E. coli pneumonia, we identified significant differences in the early cellular and molecular dynamics in the lungs that likely contribute to the elevated susceptibility of neonates to bacterial pneumonia and could represent targets for intervention to improve respiratory outcomes and survivability of neonates | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a E. coli | |
| 650 | 4 | |a immunology | |
| 650 | 4 | |a infectious disease | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a juvenile | |
| 650 | 4 | |a lungs | |
| 650 | 4 | |a macrophage | |
| 650 | 4 | |a microbiology | |
| 650 | 4 | |a monocyte | |
| 650 | 4 | |a mouse | |
| 650 | 4 | |a neonatal | |
| 650 | 4 | |a pneumonia | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 700 | 1 | |a Venezia, Jarrett |e verfasserin |4 aut | |
| 700 | 1 | |a Ndeh, Roland |e verfasserin |4 aut | |
| 700 | 1 | |a Michki, Nigel |e verfasserin |4 aut | |
| 700 | 1 | |a Perez, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Singer, Benjamin David |e verfasserin |4 aut | |
| 700 | 1 | |a Cimbro, Raffaello |e verfasserin |4 aut | |
| 700 | 1 | |a Soloski, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Alan L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t eLife |d 2012 |g 12(2023) vom: 02. Juni |w (DE-627)NLM221831460 |x 2050-084X |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2023 |g day:02 |g month:06 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.7554/eLife.82933 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2023 |b 02 |c 06 | ||