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Interleukin-33 facilitates neutrophil recruitment and bacterial clearance in S. aureus-caused peritonitis
Affiliation:1. Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China;2. Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China;3. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China;4. Intensive Care Unit, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China;1. Normandie University, SMS EA3233, University of Rouen, rue Lucien Tesnière, 76821, Mont Saint Aignan Cedex, France;2. Sanofi R&D, Lead Generation and Compound Realization/Analytical Sciences/Solid State group, F-94400 Vitry sur Seine, France;3. Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, ETSEIB, 08028 Barcelona, Spain;4. Caractérisation des Matériaux à Activité Thérapeutique (CAMMAT), Faculté de Pharmacie de l’Université Paris Descartes, F-75006 Paris, France;1. Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People''s Hospital, Shanghai, China;2. Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People''s Hospital, Shanghai, China;3. Department of Cardiology, Jinzhou Central Hospital, Jinzhou, China;4. Graduate School of Nanchang University, Nanchang, China;1. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;2. Sachs'' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden;3. Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;4. Clinical Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;5. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;6. Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden;1. Federal Institute for Drugs and Medical Devices, L2-Biosafety-Laboratory;2. Federal Institute for Drugs and Medical Devices, Biostatistics Unit, Bonn;3. Robert Koch Institute, Wernigerode, Germany
Abstract:Interleukin (IL)-33, a newly recognized member of IL-1 family of cytokines, plays an important role in polarizing Th2-associated immunity. Recently growing evidence indicates that IL-33 also represents a crucial mediator of antimicrobial infection. In this study, we investigated the effect of IL-33 on antibacterial response using an acute Staphylococcus aureus peritoneal infection model. Our results showed that IL-33 administration induced a rapid bacterial clearance and markedly reduced the S. aureus infection-related mortality. IL-33-treated mice displayed increased neutrophil influx into the focus of infection and higher concentrations of chemokine CXCL2 in the peritoneum than untreated mice. The beneficial effect of IL-33 priming was related to reversal of the S. aureus-induced reduction of CXCR2 expression on the surface of neutrophils. Furthermore, conditioning of neutrophils by IL-33 led to the enhancement of complement receptor 3 expression induced by S. aureus, which in turn facilitates the phagocytosis of opsonized S. aureus. Finally, neutrophils primed by IL-33 upregulated the production of reactive oxygen species and the subsequent killing activity for S. aureus. All together, these findings suggest that IL-33, through regulating multiple steps of neutrophil-mediated bactericidal function, provides a profound effect in host antimicrobial defense response.
Keywords:Interleukin-33  Peritonitis  Neutrophils  Phagocytosis  Reactive oxygen species
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