| Autor: |
Osman IO; Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, 13005 Marseille, France., Caputo A; Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, 13005 Marseille, France., Pinault L; Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, 13005 Marseille, France., Mege JL; Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, 13005 Marseille, France.; Laboratory of Immunology, Assitance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France., Levasseur A; Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, 13005 Marseille, France., Devaux CA; Microbes Evolution Phylogeny and Infection (MEPHI) Laboratory, Aix-Marseille University, Institut de Recherche Pour le Développement (IRD), Assistance Publique Hôpitaux de Marseille (APHM), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, 13005 Marseille, France.; Centre National de la Recherche Scientifique (CNRS), 13009 Marseille, France. |
| Abstrakt: |
Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by C. burnetii leads to modulation of the E-cad/β-cat pathway, our purpose was to identify which sheddase(s) might catalyze the cleavage of E-cad. Here, we searched for a direct mechanism of cleavage initiated by the bacterium itself, assuming the possible synthesis of a sheddase encoded in the genome of C. burnetii or an indirect mechanism based on the activation of a human sheddase. Using a straightforward bioinformatics approach to scan the complete genomes of four laboratory strains of C. burnetii , we demonstrate that C. burnetii encodes a 451 amino acid sheddase (CbHtrA) belonging to the HtrA family that is differently expressed according to the bacterial virulence. An artificial CbHtrA gene (CoxbHtrA) was expressed, and the CoxbHtrA recombinant protein was found to have sheddase activity. We also found evidence that the C. burnetii infection triggers an over-induction of the human HuHtrA gene expression. Finally, we demonstrate that cleavage of E-cad by CoxbHtrA on macrophages-THP-1 cells leads to an M2 polarization of the target cells and the induction of their secretion of IL-10, which "disarms" the target cells and improves C. burnetii replication. Taken together, these results demonstrate that the genome of C . burnetii encodes a functional HtrA sheddase and establishes a link between the HtrA sheddase-induced cleavage of E-cad, the M2 polarization of the target cells and their secretion of IL-10, and the intracellular replication of C. burnetii . |
