Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor

Cundell, Diana R.; Gerard, Norma P.; Gérard, Craig; Idänpään‐Heikkilä, Ilona; Tuomanen, Elaine

doi:10.1038/377435a0

Cited by 678 publications

(671 citation statements)

References 29 publications

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“…6A). This defect in adherence to cytokine-activated cells was consistent with the absence of adherence of the mutant to the purified glycoconjugates, sialic acid and lacto-N-neotetraose (Cundell et al, 1995b), which are known to be receptors for pneumococci on cytokine-activated cells (Fig. 6B).…”

Section: Analysis Of Cbpa-defective Mutantsmentioning

confidence: 49%

“…Together with the ability of purified CBPs to inhibit pneumococcal attachment, these results suggest that CbpA may be a structural adhesin with potential lectin activity. Cytokine-activated cells are proposed as expressing the platelet-activating factor (PAF) receptor, which may bind the phosphorylcholine of the pneumococcal cell wall (Cundell et al, 1995b). The presence of CBPs attached to the phosphorylcholine would presumably mask phosphorylcholine binding to the PAF receptor.…”

Section: Discussionmentioning

confidence: 99%

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Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Rosenow

Ryan

Weiser

et al. 1997

Molecular Microbiology

436

465

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SummaryThe surface of Streptococcus pneumoniae is decorated with a family of choline-binding proteins (CBPs) that are non-covalently bound to the phosphorylcholine of the teichoic acid. Two examples (PspA, a protective antigen, and LytA, the major autolysin) have been well characterized. We identified additional CPBs and characterized a new CBP, CbpA, as an adhesin and a determinant of virulence. Using choline immobilized on a solid matrix, a mixture of proteins from a pspA-deficient strain of pneumococcus was eluted in a choline-dependent fashion. Antisera to these proteins passively protected mice challenged in the peritoneum with a lethal dose of pneumococci. The predominant component of this mixture, CbpA, is a 75-kDa surface-exposed protein that reacts with human convalescent antisera. The deduced sequence from the corresponding gene showed a chimeric architecture with a unique N-terminal region and a C-terminal domain consisting of 10 repeated choline-binding domains nearly identical to PspA. A cbpA-deficient mutant showed a >50% reduction in adherence to cytokine-activated human cells and failed to bind to immobilized sialic acid or lacto-N-neotetraose, known pneumococcal ligands on eukaryotic cells. Carriage of this mutant in an animal model of nasopharyngeal colonization was reduced 100-fold. There was no difference between the parent strain and this mutant in an intraperitoneal model of sepsis. These data for CbpA extend the important functions of the CBP family to bacterial adherence and identify a pneumococcal vaccine candidate.

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Section: Analysis Of Cbpa-defective Mutantsmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Rosenow

Ryan

Weiser

et al. 1997

Molecular Microbiology

436

465

View full text Add to dashboard Cite

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“…14 However, in preliminary experiments, we could not identify such a role for CD44 in phagocytosis of S. pneumoniae (data not shown). Moreover, increased dissemination of pneumococci in the presence of CD44 could in theory also be a result of the bacteria using CD44 to overcome the epithelial-endothelial barrier, a mechanism that has previously been described for pneumocci and the plateletactivating factor receptor, 33,34 but also for urothelial CD44 and E. coli through binding of HA. 11 However, we could not demonstrate an interaction between CD44 and S. pneumoniae either directly or indirectly through HA (data not shown).…”

Section: Discussionmentioning

confidence: 99%

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

Windt

Hoogendijk

Vos

et al. 2011

Laboratory Investigation

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Streptococcus pneumoniae is the most prevalent pathogen causing community-acquired pneumonia. CD44 is a transmembrane adhesion molecule, expressed by a wide variety of cell types, that has several functions in innate and adaptive immune responses. In this study, we tested the hypothesis that CD44 is involved in the host response during pneumococcal pneumonia. On intranasal infection with a lethal dose of S. pneumoniae CD44-knockout (KO) mice showed a prolonged survival when compared with wild-type mice, which was accompanied by a diminished pulmonary bacterial growth and reduced dissemination to distant body sites. Whereas, proinflammatory cytokine responses and lung pathology were not affected, CD44 deficiency resulted in increased early neutrophil influx into the lung. In separate experiments, we confirmed a detrimental role of CD44 in host defense against pneumococci during sublethal pneumonia, as demonstrated by an improved capacity of CD44 KO mice to clear a low infectious dose. In addition, CD44 appeared important for the resolution of lung inflammation during sublethal pneumonia, as shown by histopathology of lung tissue slides. In conclusion, we show here that CD44 facilitates bacterial outgrowth and dissemination during pneumococcal pneumonia, which in lethal infection results in a prolonged survival of CD44 KO mice. Moreover, during sublethal pneumonia CD44 contributes to the resolution of the inflammatory response.

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“…In contrast, PAFR activation may underlie the tissue injury in the lungs (11)(12)(13). In addition, the PAFR can bind phosphorylcholine, which is not only a biologically important component of its natural ligand PAF but also part of the cell wall of a number of respiratory pathogens, including Streptococcus pneumoniae (14,15) and Haemophilus influenzae (16); in the case of pneumococcal pneumonia, the interaction between phosphorylcholine and the PAFR facilitates bacterial invasion (17,18), whereas it does not impact on host defense during H. influenzae pneumonia (19). Lung injury associated with P. aeruginosa infection results from both the direct destructive effects of the bacterium on the lung parenchyma as well as from excessive host immune responses (2).…”

mentioning

confidence: 99%

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

Zoelen

Florquin²,

Meijers

et al. 2008

The Journal of Immunology

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Pseudomonas aeruginosa is a major cause of nosocomial pneumonia, which is associated with high morbidity and mortality. Because of its ubiquitous nature and its ability to develop resistance to antibiotics, it is a problematic pathogen from a treatment perspective. Platelet-activating factor receptor (PAFR) is involved in phagocytosis of several pathogens. To determine the role of PAFR in the innate immune response to P. aeruginosa pneumonia, pafr gene-deficient (PAFR−/−) mice and normal wild-type (Wt) mice were intranasally inoculated with P. aeruginosa. PAFR deficiency impaired host defense as reflected by increased bacterial outgrowth and dissemination in mice with a targeted deletion of the PAFR gene. PAFR−/− neutrophils showed a diminished phagocytosing capacity of P. aeruginosa in vitro. Relative to Wt mice, PAFR−/− mice demonstrated increased lung inflammation and injury as reflected by histopathology, relative lung weights and total protein concentrations in bronchoalveolar lavage fluid, which was accompanied by higher levels of proinflammatory cytokines in lung homogenates and plasma. In addition, PAFR deficiency was associated with exaggerated local and systemic activation of coagulation as determined by fibrin staining of lung tissue and pulmonary and plasma concentrations of thrombin-antithrombin complexes and D-dimer. These data suggest that PAFR is an essential component of an effective host response to P. aeruginosa pneumonia, at least partly via its contribution to the phagocytic properties of professional granulocytes. Additionally, our results indicate that PAFR signaling is not essential for the induction of a local and systemic inflammatory and procoagulant response to Pseudomonas pneumonia.

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Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor

Cited by 678 publications

References 29 publications

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

The role of CD44 in the acute and resolution phase of the host response during pneumococcal pneumonia

Platelet-Activating Factor Receptor Contributes to Host Defense against Pseudomonas aeruginosa Pneumonia but Is Not Essential for the Accompanying Inflammatory and Procoagulant Response

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