Macrophage Depletion in CCR2-/- Mice Delays Bacterial Clearance and Enhances Neutrophil Infiltration in an Acute Otitis Media Model.
Animals
Bacterial Infections
/ etiology
Biomarkers
Disease Models, Animal
Disease Susceptibility
Gene Expression Profiling
Haemophilus Infections
/ etiology
Haemophilus influenzae
/ immunology
Macrophages
/ immunology
Mice
Mice, Knockout
Neutrophil Infiltration
/ immunology
Otitis Media
/ etiology
Receptors, CCR2
/ deficiency
CCR2
chlodronate liposome
macrophages
otitis media
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
31
03
2020
accepted:
17
06
2020
pubmed:
24
6
2020
medline:
7
9
2021
entrez:
24
6
2020
Statut:
ppublish
Résumé
Otitis media (OM) is a common and potentially serious disease of childhood. Although OM is multifactorial on origin, bacterial infection is a unifying component. Many studies have established a critical role for innate immunity in bacterial clearance and OM resolution. A key component of innate immunity is the recruitment of immune and inflammatory cells, including macrophages. To explore the role of macrophages in OM, we evaluated the expression of genes related to macrophage function during a complete episode of acute OM in the mouse caused by middle ear (ME) inoculation with Haemophilus influenzae. We also combined CCR2 deficiency with chlodronate liposome toxicity to deplete macrophages during OM. Macrophage genes were robustly regulated during OM. Moreover, macrophage depletion enhanced and prolonged the infiltration of neutrophils into the infected ME and increased the persistence of bacterial infection. The results illustrate the critical role played by macrophages in OM resolution.
Sections du résumé
BACKGROUND
Otitis media (OM) is a common and potentially serious disease of childhood. Although OM is multifactorial on origin, bacterial infection is a unifying component. Many studies have established a critical role for innate immunity in bacterial clearance and OM resolution. A key component of innate immunity is the recruitment of immune and inflammatory cells, including macrophages.
METHODS
To explore the role of macrophages in OM, we evaluated the expression of genes related to macrophage function during a complete episode of acute OM in the mouse caused by middle ear (ME) inoculation with Haemophilus influenzae. We also combined CCR2 deficiency with chlodronate liposome toxicity to deplete macrophages during OM.
RESULTS
Macrophage genes were robustly regulated during OM. Moreover, macrophage depletion enhanced and prolonged the infiltration of neutrophils into the infected ME and increased the persistence of bacterial infection.
CONCLUSIONS
The results illustrate the critical role played by macrophages in OM resolution.
Identifiants
pubmed: 32572481
pii: 5861006
doi: 10.1093/infdis/jiaa353
pmc: PMC7857354
doi:
Substances chimiques
Biomarkers
0
Ccr2 protein, mouse
0
Receptors, CCR2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
333-341Subventions
Organisme : NIDCD NIH HHS
ID : R03 DC014801
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC012595
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC000129
Pays : United States
Organisme : BLRD VA
ID : I01 BX001205
Pays : United States
Informations de copyright
Published by Oxford University Press for the Infectious Diseases Society of America 2020.