Inhaltszusammenfassung

Objective: Bacterial signal peptides trigger innate immune responses via formyl peptide receptors (FPRs), present in immune cells. We investigated their effects on mucociliary clearance, which is a major defense mechanism against invasive bacteria in the trachea. Methods: The trachea of C57Bl6, TRPM5- (transient receptor potential channel 5), PLCβ2-deficient mice (phospholipase Cβ2) (two crucial components of the canonical taste transduction cascade) and FVB/NCrl mice was explanted ... Objective: Bacterial signal peptides trigger innate immune responses via formyl peptide receptors (FPRs), present in immune cells. We investigated their effects on mucociliary clearance, which is a major defense mechanism against invasive bacteria in the trachea. Methods: The trachea of C57Bl6, TRPM5- (transient receptor potential channel 5), PLCβ2-deficient mice (phospholipase Cβ2) (two crucial components of the canonical taste transduction cascade) and FVB/NCrl mice was explanted and particle transport speed (PTS) was visualized by tracking directed transport of dynabeads. The transcriptome of single tracheal ciliated and brush cells, a cholinergic chemosensory epithelial cell type, was analyzed by single cell deep sequencing. Results: Deep sequencing of single epithelial cells showed FPR expression in both ciliated and brush cells. The N-formylated bacterial signal peptide FL185 (10µM), a product of pathogenic bacteria (e.g. E. coli), increased PTS from 45 ± 2 to 73 ± 3 µm/s (mean ± SEM). Specific FPR1 and FPR2 inhibitors [cyclosporine H (1µM) and t-BOC2 (10µM)] did not reduce the effect, it was also conserved in FVB/NCrl mice lacking a functional FPR3. In contrast, FL185 was ineffective to increase PTS in TRPM5- and PLCβ2-deficient mice. Atropine (1µM), a muscarinic antagonist, diminished the effect of FL185. Conclusion: A bacterial signal peptide of pathogenic origin stimulates cilia-driven mucociliary clearance. Rather than being mediated by FPR, this mechanism depends on classical taste transduction cascade components which are uniquely coexpressed in the trachea by brush cells, and subsequent cholinergic signaling to ciliated cells. We interpret this as a novel defense mechanism against bacteria. » weiterlesen» einklappen

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Klassifikation

DFG Fachgebiet:
Medizin

DDC Sachgruppe:
Biowissenschaften, Biologie