Sialoglycoproteins adsorbed byPseudomonas aeruginosafacilitate their survival by impeding neutrophil extracellular trap through siglec-9
- 1 April 2012
- journal article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 91 (4), 641-655
- https://doi.org/10.1189/jlb.0511260
Abstract
PA is an opportunistic pathogen that is commonly associated with severe infection in immunocompromised hosts. Siglec-9 binds with Sias by cis interaction on the neutrophil surface, thereby reducing immunological activity. However, neutrophils bind with pathogens through trans interactions of siglec-9 with Sias. Neutrophils kill invading pathogens by NETs, along with extracellular phagocytosis. Here, we report the mode of the adsorption of Sias by PA from host serum, the interaction of PA+Sias with human neutrophils, and the resulting neutrophil immunological activity. The α2–3-linked sialoglycoproteins adsorbed by PA exhibited potent binding with the soluble siglec-9-Fc chimeras, CHO-siglec-9 and siglec-9 on neutrophils. The binding between PA+Sias and neutrophils was blocked by the synthetic sialoglycan Neu5Acα2–3Galβ1–4GlcNAc, confirming the linkage-specific, Sias–siglec-9 interaction. The PA+Sias and siglec-9 interaction on neutrophils reduced the level of ROS and the release of elastase, resulting in a reduction of NETs formation, demonstrating the role of the sialoglycoproteins adsorbed by PA in the weakening of neutrophil activity. The resistance of PA+Sias to NETs was made evident by the increased survival of PA+Sias. Moreover, the decrease in PA−Sias survival demonstrated the involvement of NETs formation in the absence of the Sias–siglec-9 interaction. N-actylcysteine or sivelestat-pretreated neutrophils enhanced the survival of PA−Sias. DNAse-pretreated neutrophils did not exhibit any NETs formation, resulting in the enhanced escape of PA−Sias. Taken together, one of the survival mechanisms of PA+Sias is the diminution of innate immunity via its adsorption of sialoglycoproteins by its engagement of the inhibitory molecule siglec-9. This is possibly a general mechanism for pathogens that cannot synthesize Sias to subvert immunity.Keywords
Funding Information
- CSIR–Indian Institute of Chemical Biology
- CSIR (IAP-0001)
- Systems Biology (HCP004)
- New Millennium Indian Technology Leadership Initiative (TLP-004)
- Department of Biotechnology under Cancer Biology (GAP 235)
- Government of India
- Indian Medical Research Council
- German Cancer Research Center
- University of Dundee
This publication has 51 references indexed in Scilit:
- Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation?Immunology, 2010
- Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular trapsThe Journal of cell biology, 2010
- Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid ANature Immunology, 2010
- PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular trapsThe Journal of Experimental Medicine, 2010
- Characterization of the Specific Interaction between Sialoadhesin and Sialylated Campylobacter jejuni LipooligosaccharidesInfection and Immunity, 2010
- Sialic acids acquired by Pseudomonas aeruginosa are involved in reduced complement deposition and siglec mediated host‐cell recognitionFEBS Letters, 2009
- Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5The Journal of Experimental Medicine, 2009
- Siglecs and their roles in the immune systemNature Reviews Immunology, 2007
- Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human LeukocytesJournal of Bacteriology, 2007
- Sialic Acid-Binding Immunoglobulin-Like Lectin 7 Mediates Selective Recognition of Sialylated Glycans Expressed on Campylobacter jejuni LipooligosaccharidesInfection and Immunity, 2006