title: Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance.
abstract: Through the use of intravital imaging of the liver, we demonstrate a collaborative role for platelets with Kupffer cells (KCs) in eradicating blood-borne bacterial infection. Under basal conditions, platelets, via the platelet-adhesion receptor GPIb, formed transient 'touch-and-go' interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria such as Bacillus cereus and methicillin-resistant Staphylococcus aureus (MRSA) were rapidly caught by KCs and triggered platelets to switch from 'touch-and-go' adhesion to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GPIbα-deficient mice had more endothelial and KC damage than did their wild-type counterparts, which led to more fluid leakage, substantial polycythemia and rapid mortality. Our study identifies a previously unknown surveillance mechanism by which platelets survey macrophages that rapidly converts to a critical host response to blood-borne bacteria.
authors.affiliation: Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada.
authors.forename: Connie H Y
authors.initials: CH
authors.lastname: Wong
authors.forename: Craig N
authors.initials: CN
authors.lastname: Jenne
authors.forename: Björn
authors.initials: B
authors.lastname: Petri
authors.forename: Navina L
authors.initials: NL
authors.lastname: Chrobok
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D001409:Bacillus cereus / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology / Q000382:microbiology*; D007113:Immunity, Innate / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology / Q000382:microbiology*; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D015539:Platelet Activation / Q000276:immunology*; D010973:Platelet Adhesiveness / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex