Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity

Steven P. Broadley, Ann Plaumann, Raffaele Coletti, Christin Lehmann, Andreas Wanisch, Amelie Seidlmeier, Knud Esser, Shanshan Luo, Patrick C. Rämer, Steffen Massberg, Dirk H. Busch, Menno van Lookeren Campagne, Admar Verschoor*

*Corresponding author for this work
    46 Citations (Scopus)

    Abstract

    Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeria monocytogenes, we show that bacterial clearance is not a uniform process but a “dual-track” mechanism consisting of parallel “fast” and “slow” pathways. “Slow clearance” is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from “fast clearance” and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8α+ dendritic cells. We consistently find “fast” and “slow” clearance patterns for a broad panel of other Gram+ and Gram− bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity.

    Original languageEnglish
    JournalCell Host and Microbe
    Volume20
    Issue number1
    Pages (from-to)36-48
    Number of pages13
    ISSN1931-3128
    DOIs
    Publication statusPublished - 13.07.2016

    Research Areas and Centers

    • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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