Inhaltszusammenfassung

Objective: Bacterial signal peptides are known to trigger innate immunity responses by activation of formyl peptide receptors (FPRs) present in immune cells, e.g. leukocytes. Members of the FPR-family are also found in the murine vomeronasal organ where they are candidates for chemosensory recognition of bacterial pathogens. Here, we investigated the effects of bacterial signal peptides on mucociliary clearance in the murine trachea. Methods: The trachea of C57Bl6, TRPM5-deficient (transi... Objective: Bacterial signal peptides are known to trigger innate immunity responses by activation of formyl peptide receptors (FPRs) present in immune cells, e.g. leukocytes. Members of the FPR-family are also found in the murine vomeronasal organ where they are candidates for chemosensory recognition of bacterial pathogens. Here, we investigated the effects of bacterial signal peptides on mucociliary clearance in the murine trachea. Methods: The trachea of C57Bl6, TRPM5-deficient (transient receptor potential cation channel subfamily M member 5; a crucial component of the canonical bitter and umami taste transduction) and FVB/NCrl mice was explanted and particle transport speed (PTS) was visualized by tracking directed transport of dynabeads at the surface. The transcriptome of single tracheal ciliated and brush cells, a chemosensory epithelial cell type, was analyzed by single cell deep sequencing. Results: Deep sequencing showed FPR expression in both ciliated and brush cells. The N-formylated bacterial signal peptide FL185 increased PTS from 43.48 ± 5.05 to 75.96 ± 3.56 µm/s (N = 8; p < 0.0001) at 10µM which addresses FPR1 – 3. Specific FPR1 and FPR2 inhibitors [cyclosporine H (1µM) and t-BOC2 (10µM)] did not reduce the effect. The effect was conserved in FVB/NCrl mice which are lacking a functional FPR3. In contrast, FL185 was ineffective in increasing PTS in TRPM5-deficient mice. Four other tested bacterial signal peptides did not increase PTS. Conclusion: A bacterial signal peptide stimulates cilia-driven mucociliary clearance, that could represent a novel defense mechanism against invasive bacteria in the trachea. This effect involves elements of the classical taste transduction cascade. » weiterlesen» einklappen

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Klassifikation

DFG Fachgebiet:
2.22 - Medizin

DDC Sachgruppe:
Biowissenschaften, Biologie