title: Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity.
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.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany; Institute for Systemic Inflammation Research, Universität zu Lübeck, 23538 Lübeck, Germany.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Broadley
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Ann
authors.initials: A
authors.lastname: Plaumann
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coletti
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Lehmann
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wanisch
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Seidlmeier
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, 81675 Munich, Germany.
authors.forename: Knud
authors.initials: K
authors.lastname: Esser
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany; Institute of Virology, Technische Universität München/Helmholtz Zentrum München, 81675 Munich, Germany.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Luo
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Rämer
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, 81377 Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, 80802 Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany; Focus Group "Clinical Cell Processing and Purification," Institute for Advanced Study, Technische Universität München, 85748 Garching, Germany; National Center for Infection Research, 81675 Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Menno
authors.initials: M
authors.lastname: van Lookeren Campagne
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany; Institute for Systemic Inflammation Research, Universität zu Lübeck, 23538 Lübeck, Germany. Electronic address: admar.verschoor@uksh.de.
authors.forename: Admar
authors.initials: A
authors.lastname: Verschoor
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D016470:Bacteremia / Q000276:immunology*; D001422:Bacterial Adhesion; D001769:Blood / Q000382:microbiology*; D001792:Blood Platelets / Q000382:microbiology*; D000069416:Intravital Microscopy; D008089:Listeria monocytogenes / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011951:Receptors, Complement / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011951:Receptors, Complement; C509992:VSIG4 protein, mouse