Enteroaggregative Escherichia coli promotes transepithelial migration of neutrophils through a conserved 12-lipoxygenase pathway

Authors

  • Erik J. Boll,

    1. Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark
    2. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
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  • Carsten Struve,

    1. Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark
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  • Anja Sander,

    1. Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark
    2. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
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  • Zachary Demma,

    1. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
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  • Karen A. Krogfelt,

    1. Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark
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  • Beth A. McCormick

    Corresponding author
    1. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
      E-mail: beth.mccormick@umassmed.edu; Tel. (+1) 508 856 6048; Fax (+1) 508 856 3355.
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E-mail: beth.mccormick@umassmed.edu; Tel. (+1) 508 856 6048; Fax (+1) 508 856 3355.

Summary

Enteroaggregative Escherichia coli (EAEC) induces release of pro-inflammatory markers and disruption of intestinal epithelial barriers in vitro, suggesting an inflammatory aspect to EAEC infection. However, the mechanisms underlying EAEC-induced mucosal inflammatory responses and the extent to which these events contribute to pathogenesis is not well characterized. Employing an established in vitro model we demonstrated that EAEC prototype strain 042 induces migration of polymorphonuclear neutrophils (PMNs) across polarized T84 cell monolayers. This event was mediated through a conserved host cell signalling cascade involving the 12/15-LOX pathway and led to apical secretion of an arachidonic acid-derived lipid PMN chemoattractant, guiding PMNs across the epithelia to the site of infection. Moreover, supporting the hypothesis that inflammatory responses may contribute to EAEC pathogenesis, we found that PMN transepithelial migration promoted enhanced attachment of EAEC 042 to T84 cells. These findings suggest that EAEC-induced PMN infiltration may favour colonization and thus pathogenesis of EAEC.

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