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Infect. Immun. doi:10.1128/IAI.01666-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Phagocytosis of Borrelia burgdorferi and Treponema pallidum potentiates innate immune activation and induces IFN- production

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

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

	Abstract

We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to a comparable extent by live Borrelia burgdorferi (Bb) and by Bb and Treponema pallidum (Tp) lysates but were poorly activated by live Tp. Because THP-1 cells poorly internalized live spirochetes, we turned to an ex vivo PBMC system that would more closely reflect spirochete-mononuclear phagocyte interactions that occur during actual infection. In this system, Bb induced significantly greater monocyte activation and inflammatory cytokine production than did borrelial lysates or Tp, and only Bb elicited IFN- from NK cells. Bb was phagocytosed avidly by monocytes while Tp was not, suggesting that the enhanced response to live Bb was due to phagocytosis of the organism. When cytochalasin D was used to block phagocytosis of live Bb, cytokine production decreased to levels comparable to those induced by Bb lysates, while the IFN- response was abrogated altogether. In the presence of human syphilitic serum, Tp was efficiently internalized and initiated responses resembling those observed with live Bb, including the production of IFN- by NK cells. Depletion of monocytes revealed they were the primary source of inflammatory cytokines, while DCs directed IFN- production from innate lymphocytes. Thus, phagocytosis of live spirochetes initiates cell activation programs in monocytes and DCs that differ qualitatively and quantitatively from those induced at the cell surface by lipoprotein-enriched lysates. The greater stimulatory capacity of Bb versus Tp appears to be explained by the successful recognition and phagocytosis of Bb by host cells and the ability of Tp to avoid detection and uptake by virtue of its denuded outer membrane rather than by differences in surface lipoprotein expression.

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