title: CRIg Functions as a Macrophage Pattern Recognition Receptor to Directly Bind and Capture Blood-Borne Gram-Positive Bacteria.
abstract: Kupffer cells (KCs), the vast pool of intravascular macrophages in the liver, help to clear blood-borne pathogens. The mechanisms by which KCs capture circulating pathogens remain unknown. Here we use intra-vital imaging of mice infected with Staphylococcus aureus to directly visualize the dynamic process of bacterial capture in the liver. Circulating S. aureus were captured by KCs in a manner dependent on the macrophage complement receptor CRIg, but the process was independent of complement. CRIg bound Staphylococcus aureus specifically through recognition of lipoteichoic acid (LTA), but not cell-wall-anchored surface proteins or peptidoglycan. Blocking the recognition between CRIg and LTA in vivo diminished the bacterial capture in liver and led to systemic bacterial dissemination. All tested Gram-positive, but not Gram-negative, bacteria bound CRIg in a complement-independent manner. These findings reveal a pattern recognition role for CRIg in the direct capture of circulating Gram-positive bacteria from the bloodstream.
authors.affiliation: The Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Zhutian
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: The Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada; Department of Medical Microbiology, University Medical Centre, Utrecht, 3584 CX, Netherlands.
authors.forename: Bas G J
authors.initials: BG
authors.lastname: Surewaard
authors.affiliation: The Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Connie H Y
authors.initials: CH
authors.lastname: Wong
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.affiliation: The Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. Electronic address: cnjenne@ucalgary.ca.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Jenne
authors.affiliation: The Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. Electronic address: pkubes@ucalgary.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000069416:Intravital Microscopy; D007728:Kupffer Cells / Q000276:immunology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000276:immunology*; D008264:Macrophages; D051379:Mice; D011485:Protein Binding; D011951:Receptors, Complement / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D013682:Teichoic Acids / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D011951:Receptors, Complement; D051192:Receptors, Pattern Recognition; D013682:Teichoic Acids; C509992:VSIG4 protein, mouse; C009900:lipoteichoic acid
keywords: Kupffer cells; Staphylococcus aureus; complement; intravital imaging; liver