Heme Oxygenase-1 Deficiency Diminishes Methicillin-Resistant Staphylococcus aureus Clearance Due to Reduced TLR9 Expression in Pleural Mesothelial Cells
| Autor: | Judith A. Johnson, Satindra Gahlot, Steven A. Sahn, Kamal A. Mohammed, Najmunnisa Nasreen |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pulmonology Staphylococcus Gene Expression lcsh:Medicine medicine.disease_cause Immune Receptors Biochemistry Mice chemistry.chemical_compound Post-Translational Modification lcsh:Science Toll-like Receptors Growth Disorders Pathology and laboratory medicine Mice Knockout Immune System Proteins Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Animal Models Medical microbiology Infectious Diseases Experimental Organism Systems Pleura Female Methicillin-resistant Staphylococcus aureus Pathogens Signal Transduction Research Article Anemia Hemolytic Staphylococcus aureus Infectious Disease Control Immunology Mouse Models Heme Biology Research and Analysis Methods Microbiology 03 medical and health sciences Model Organisms In vivo Immunity Genetics medicine Animals Medicine and health sciences Innate immune system Biology and life sciences Bacteria 030102 biochemistry & molecular biology Zinc protoporphyrin lcsh:R Organisms Proteins TLR9 Epithelial Cells Cell Biology Pneumonia biochemical phenomena metabolism and nutrition medicine.disease bacterial infections and mycoses Iron Metabolism Disorders Immunity Innate Empyema Microbial pathogens 030104 developmental biology chemistry Toll-Like Receptor 9 TLR4 Bacterial pathogens lcsh:Q Heme Oxygenase-1 |
| Zdroj: | PLoS ONE, Vol 12, Iss 1, p e0169245 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Methicillin Resistant Staphylococcus aureus (MRSA) cause pneumonia and empyema thoraces. TLR9 activation provides protection against bacterial infections and Heme oxygenase-1 (HO-1) is known to enhance host innate immunity against bacterial infections. However, it is still unclear whether HO-1 regulates TLR-9 expression in the pleura and modulates the host innate defenses during MRSA empyema. In order to determine if HO-1 regulates host innate immune functions via modulating TLR expression, in MRSA empyema, HO-1+/+ and HO-1-/- mouse pleural mesothelial cells (PMCs) were infected with MRSA (1:10, MOI) in the presence or absence of Cobalt Protoporphyrin (CoPP) and Zinc Protoporphyrin (ZnPP) or CORM-2 (a Carbon monoxide donor) and the expression of mTLR9 and mBD14 was assessed by RT-PCR. In vivo, HO-1+/+ and HO-1-/- mice were inoculated with MRSA (5x106 CFU) intra-pleurally and host bacterial load was measured by CFU, and TLR9 expression in the pleura was determined by histochemical-immunostaining. We noticed MRSA inducing differential expression of TLR9 in HO-1+/+ and HO-1 -/- PMCs. In MRSA infected HO-1+/+ PMCs, TLR1, TLR4, and TLR9 expression was several fold higher than MRSA infected HO-1-/- PMCs. Particularly TLR9 expression was very low in MRSA infected HO-1-/- PMCs both in vivo and in vitro. Bacterial clearance was significantly higher in HO-1+/+ PMCs than compared to HO-1-/- PMCs in vitro, and blocking TLR9 activation diminished MRSA clearance significantly. In addition, HO-1-/- mice were unable to clear the MRSA bacterial load in vivo. MRSA induced TLR9 and mBD14 expression was significantly high in HO-1+/+ PMCs and it was dependent on HO-1 activity. Our findings suggest that HO-1 by modulating TLR9 expression in PMCs promotes pleural innate immunity in MRSA empyema. |
| Databáze: | OpenAIRE |
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