PloS one, 2016-03, Vol.11 (3), p.e0149233-e0149233
2016
Details
- Autor(en) / Beteiligte
- Titel
- Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4
- Ist Teil von
- PloS one, 2016-03, Vol.11 (3), p.e0149233-e0149233
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0149233Titel-ID: cdi_plos_journals_1773263305
- Format
- –
- Schlagworte
- Analysis, Animals, Antibiotics, Antimicrobial agents, Bacteria, Bacterial infections, Bacterial pneumonia, Bactericidal activity, Biology and Life Sciences, Bronchus, Complement receptors, Cytokines, Cytokines - immunology, Dosage and administration, Drug resistance, Drug therapy, Ethics, Health aspects, Hospitals, Immune clearance, Immune response, Immune system, Immunoglobulins, Immunology, Immunotherapy, Infections, Infiltration, Inflammation, Innate immunity, Interleukin 10, Interleukin 6, Lactoferrin, Lactoferrins, Leukocytes (neutrophilic), Ligands, Lipopeptides - pharmacology, Lungs, Macrophage-1 Antigen - immunology, Medical laboratories, Medicine and Health Sciences, Methicillin, Methicillin-Resistant Staphylococcus aureus - immunology, Mice, Mortality, mRNA, Neutrophils, Pathogens, Pattern recognition, Pattern recognition receptors, Phagocytosis, Pneumonia, Pneumonia, Staphylococcal - drug therapy, Pneumonia, Staphylococcal - immunology, Pneumonia, Staphylococcal - pathology, Proteins, Receptors, Receptors, Complement 3b - immunology, Receptors, IgG - immunology, Research and Analysis Methods, Sepsis, Staphylococcus aureus, Staphylococcus aureus infections, Staphylococcus infections, Studies, TLR2 protein, Toll-Like Receptor 2 - agonists, Toll-Like Receptor 2 - immunology, Toll-like receptors, Tumor necrosis factor-α