Immunostimulatory Effect of Flagellin on MDR-Klebsiella-Infected Human Airway Epithelial Cells

Pneumonia caused by multi-drug-resistant Klebsiella pneumoniae (MDR-Kpneu) poses a major public health threat, especially to immunocompromised or hospitalized patients. This study aimed to determine the immunostimulatory effect of the Toll-like receptor 5 ligand flagellin on primary human lung epithelial cells during infection with MDR-Kpneu. Human bronchial epithelial (HBE) cells, grown on an air-liquid interface, were inoculated with MDR-Kpneu on the apical side and treated during ongoing infection with antibiotics (meropenem) and/or flagellin on the basolateral and apical side, respectively; the antimicrobial and inflammatory effects of flagellin were determined in the presence or absence of meropenem. In the absence of meropenem, flagellin treatment of MDR-Kpneu-infected HBE cells increased the expression of antibacterial defense genes and the secretion of chemokines; moreover, supernatants of flagellin-exposed HBE cells activated blood neutrophils and monocytes. However, in the presence of meropenem, flagellin did not augment these responses compared to meropenem alone. Flagellin did not impact the outgrowth of MDR-Kpneu. Flagellin enhances antimicrobial gene expression and chemokine release by the MDR-Kpneu-infected primary human bronchial epithelium, which is associated with the release of mediators that activate neutrophils and monocytes. Topical flagellin therapy may have potential to boost immune responses in the lung during pneumonia.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

International journal of molecular sciences - 25(2023), 1 vom: 25. Dez.

Sprache:

Englisch

Beteiligte Personen:

van Linge, Christine C A [VerfasserIn]
Hulme, Katina D [VerfasserIn]
Peters-Sengers, Hessel [VerfasserIn]
Sirard, Jean-Claude [VerfasserIn]
Goessens, Wil H F [VerfasserIn]
de Jong, Menno D [VerfasserIn]
Russell, Colin A [VerfasserIn]
de Vos, Alex F [VerfasserIn]
van der Poll, Tom [VerfasserIn]

Links:

Volltext

Themen:

12777-81-0
Anti-Bacterial Agents
Antibiotics
FV9J3JU8B1
Flagellin
Human bronchial epithelial cells
Journal Article
Klebsiella pneumoniae
Meropenem
Multi-drug resistance
Pneumonia

Anmerkungen:

Date Completed 12.01.2024

Date Revised 13.01.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms25010309

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366940570