title: Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcus pneumoniae infection.
abstract: The dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) homolog, SIGN-related 1 (SIGNR1) is a pathogen receptor expressed by splenic marginal zone and peritoneal macrophages, and is essential for clearance of Streptococcus pneumoniae by phagocytosis after intraperitoneal infection. Here, we identified an important in vivo function for SIGNR1 in S. pneumonia infection induced via its natural entrance route. Upon intranasal infection with S. pneumoniae, SIGNR1-deficient mice did not clear bacteria from lung and blood, and displayed severely enhanced inflammatory parameters compared to the wild-type mice. However, SIGNR1 is not expressed by alveolar macrophages, suggesting that another mechanism than a decrease in phagocytosis is responsible for this difference. Natural anti-phosphorylcholine IgM produced by marginal zone B cells is essential for protection against infection with S. pneumoniae. Strikingly, during infection, SIGNR1-deficient mice failed to produce a rapid anti-phosphorylcholine IgM response. Marginal zone macrophages have been suggested to capture antigens for presentation to marginal zone B cells. We demonstrate that marginal zone macrophages from SIGNR1-deficient mice in contrast to wild-type mice are not able to capture pneumococci from blood, suggesting that SIGNR1 on marginal zone macrophages captures S. pneumoniae for antigen presentation to and activation of marginal zone B cells, resulting in an anti-phosphorylcholine IgM response.
authors.affiliation: Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Estella A
authors.initials: EA
authors.lastname: Koppel
authors.forename: Catharina W
authors.initials: CW
authors.lastname: Wieland
authors.forename: Venice C M
authors.initials: VC
authors.lastname: van den Berg
authors.forename: Manja
authors.initials: M
authors.lastname: Litjens
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000172:deficiency / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010767:Phosphorylcholine / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000276:immunology*; D013296:Streptococcus pneumoniae; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M; D037181:Lectins, C-Type; D010767:Phosphorylcholine; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin