title: PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease.
abstract: Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium--the amidase LytA--were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1-/- mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1-/- mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease.
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ramos-Sevillano
authors.affiliation: Department of Immunology, Instituto Investigación Sanitaria Princesa (IIS-IP), Hospital de la Princesa, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Urzainqui
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: de Andrés
authors.affiliation: Department of Immunology, Instituto Investigación Sanitaria Princesa (IIS-IP), Hospital de la Princesa, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: González-Tajuelo
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Domenech
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: González-Camacho
authors.affiliation: Department of Immunology, Instituto Investigación Sanitaria Princesa (IIS-IP), Hospital de la Princesa, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: Centre for Inflammation and Tissue Repair, University College London, London, United Kingdom.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Brown
authors.affiliation: Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: García
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Yuste
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D018805:Sepsis / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D009238:N-Acetylmuramoyl-L-alanine Amidase