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Infect. Immun. doi:10.1128/IAI.01039-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Phagocytosis of Borrelia burgdorferi, the Lyme disease spirochete, potentiates innate immune activation and induces apoptosis in human monocytes

Departments of Medicine, and Genetics and Developmental Biology; University of Connecticut Health Center, Farmington, CT 06030-3715 and Department of Pediatrics, Division of Infectious Diseases, Connecticut Children's Medical Center, Hartford, CT 06106

^* To whom correspondence should be addressed. Email: JRadolf{at}up.uchc.edu.

	Abstract

We have previously demonstrated that phagocytosed Borrelia burgdorferi (Bb) induce activation programs in human peripheral blood mononuclear cells that differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report that ingested Bb induce significantly greater transcription of proinflammatory cytokine genes and that live Bb, but not lysates, are avidly internalized by monocytes where they are completely degraded within phagolysosomes. In the course of these experiments, we discovered that live Bb also induced a dose-dependent decrease in monocytes, but not in dendritic cells or T cells, and that the monocyte population displayed morphological and biochemical hallmarks of apoptosis. Particularly noteworthy was that apoptotic changes occurred predominantly in monocytes that had internalized spirochetes. Abrogation of phagocytosis with cytochalasin D prevented the death response. Heat-killed Bb, which was internalized as well as live organisms, induced a similar degree of apoptosis of monocytes but markedly less cytokine production. Surprisingly, opsonophagocytosis of Treponema pallidum did not elicit a discernible cell death response. Our combined results demonstrate that Bb confined to phagolysosomes are potent inducers of cytosolic signals that result in (i) production of NF-B-dependent cytokines; (ii) assembly of the inflammasome and activation of caspase-1; and (iii) induction of programmed cell death. We propose that inflammation and apoptosis represent mutually reinforcing components of the immunologic arsenal that the host mobilizes to defend itself against infection with Lyme disease spirochetes.

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