Complement receptor 3 and Toll-like receptor 4 act sequentially in uptake and intracellular killing of unopsonized Salmonella enterica serovar Typhimurium by human neutrophils
| Autor: | Jaap T. van Dissel, Robin van Bruggen, Dirk Roos, Taco W. Kuijpers, Angela van Diepen, Debby Zweers, Arthur J. Verhoeven |
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| Přispěvatelé: | Landsteiner Laboratory, Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Salmonella typhimurium
Salmonella Neutrophils Immunology Cell Culture Techniques Macrophage-1 Antigen medicine.disease_cause Microbiology Neutrophil Activation medicine Humans Receptor Toll-like receptor Cellular Microbiology: Pathogen-Host Cell Molecular Interactions NADPH oxidase biology biology.organism_classification Toll-Like Receptor 4 Infectious Diseases Salmonella enterica Macrophage-1 antigen Salmonella Infections biology.protein TLR4 Parasitology Intracellular |
| Zdroj: | Infection and immunity, 75(6), 2655-2660. American Society for Microbiology |
| ISSN: | 0019-9567 |
| Popis: | The uptake and subsequent killing ofSalmonella entericaserovar Typhimurium by human neutrophils was studied. In particular, two pattern recognition receptors, complement receptor 3 (CR3) and Toll-like receptor 4 (TLR4), were found to be essential for the efficient uptake and activation, respectively, of the NADPH oxidase. The uptake ofSalmonellawas almost completely inhibited by various monoclonal antibodies against CR3, and neutrophils from a patient with leukocyte adhesion deficiency type 1, which lack CR3, showed almost no uptake ofSalmonella. A lipopolysaccharide (LPS) mutant strain ofSalmonellawas used to show that the expression of full-length, wild-type, or so-called smooth LPS is important for the efficient killing of intracellularSalmonella. Infection with wild-type-LPS-expressingSalmonellaresulted in the generation of reactive oxygen species (ROS) in TLR4-decorated,Salmonella-containing vacuoles, whereas ROS were not induced by an LPS mutant strain. In addition, the recognition ofSalmonellaby neutrophils, leading to ROS production, was shown to be intracellular, as determined by priming experiments with intact bacteria under conditions where the bacterium is not taken up. Finally, the generation of ROS in the wild-type-Salmonella-infected neutrophils was largely inhibited by the action of a TLR4-blocking, cell-permeable peptide, showing that signaling by this receptor from theSalmonella-containing vacuole is essential for the activation of the NADPH oxidase. In sum, our data identify the sequential recognition of unopsonizedSalmonellastrains by CR3 and TLR4 as essential events in the efficient uptake and killing of this intracellular pathogen. |
| Databáze: | OpenAIRE |
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