Flagellar Hooks and Hook Protein FlgE Participate in Host Microbe Interactions at Immunological Level
Abstract Host-microbe interactions determine the outcome of host responses to commensal and pathogenic microbes. Previously, two epithelial cell-binding peptides were found to be homologues of two sites (B, aa168–174; F, aa303–309) in the flagellar hook protein FlgE of Pseudomonas aeruginosa. Tertia...
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| Autores principales: | , , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/7ebbf896e5934f6cb3c71d42c3319adf |
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| Sumario: | Abstract Host-microbe interactions determine the outcome of host responses to commensal and pathogenic microbes. Previously, two epithelial cell-binding peptides were found to be homologues of two sites (B, aa168–174; F, aa303–309) in the flagellar hook protein FlgE of Pseudomonas aeruginosa. Tertiary modeling predicted these sites at the interface of neighboring FlgE monomers in the fully formed hook. Recombinant FlgE protein stimulated proinflammatory cytokine production in a human cell line and in murine lung organoid culture as detected with real-time RT-PCR and ELISA assays. When administered to mice, FlgE induced lung inflammation and enhanced the Th2-biased humoral response to ovalbumin. A pull-down assay performed with FlgE-saturated resin identified caveolin-1 as an FlgE-binding protein, and caveolin-1 deficiency impaired FlgE-induced inflammation and downstream Erk1/2 pathway activation in lung organoids. Intact flagellar hooks from bacteria were also proinflammatory. Mutations to sites B and F impaired bacteria motility and proinflammatory potency of FlgE without altering adjuvanticity of FlgE. These findings suggest that the flagellar hook and FlgE are novel players in host-bacterial interactions at immunological level. Further studies along this direction would provide new opportunities for understanding and management of diseases related with bacterial infection. |
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