Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6803
PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease
Ramos-Sevillano, Elisa ISCIII | Urzainqui, Ana | Andres, Belen de ISCIII | González-Tajuelo, Rafael | Domenech Lucas, Mirian ISCIII | Gonzalez-Camacho, Fernando ISCIII | Sanchez-Madrid, Francisco CNIC | Brown, Jeremy S | García, Ernesto | Yuste, Jose Enrique ISCIII
PLoS Pathog. 2016 Mar 14;12(3):e1005500
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.
Animals | Disease Models, Animal | Female | Humans | Leukocytes | Lung | Macrophages | Membrane Glycoproteins | Mice | Mice, Inbred C57BL | N-Acetylmuramoyl-L-alanine Amidase | Neutrophils | Phagocytosis | Pneumococcal Infections | Pneumonia, Pneumococcal | Sepsis | Streptococcus pneumoniae
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