TLR4-interacting SPA4 peptide improves host defense and alleviates tissue injury in a mouse model of Pseudomonas aeruginosa lung infection
| Autor: | Jun Xie, Shanjana Awasthi, Bhupinder Singh, Vijay Ramani, Stanley D. Kosanke |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Chemokine Peptide Pathology and Laboratory Medicine medicine.disease_cause Immune Receptors Biochemistry Mice Database and Informatics Methods 0302 clinical medicine Animal Cells Phagosomes Medicine and Health Sciences Immune Response Toll-like Receptors Cells Cultured chemistry.chemical_classification Immune System Proteins Multidisciplinary Pulmonary Surfactant-Associated Protein A biology Chemistry Pseudomonas Aeruginosa Animal Models Bacterial Pathogens 3. Good health Experimental Organism Systems Medical Microbiology Cell Processes 030220 oncology & carcinogenesis Medicine Female Inflammation Mediators Pathogens Anatomy Cellular Types medicine.symptom Sequence Analysis Protein Binding Signal Transduction Research Article Bioinformatics Immune Cells Science Immunology Antigen-Presenting Cells Mouse Models Inflammation Research and Analysis Methods Microbiology Proinflammatory cytokine 03 medical and health sciences Model Organisms Signs and Symptoms Immune system Phagocytosis Amino Acid Sequence Analysis Diagnostic Medicine Pseudomonas Pneumonia Bacterial medicine Animals Pseudomonas Infections Microbial Pathogens Bacteria Pseudomonas aeruginosa Intracellular parasite Organisms Biology and Life Sciences Proteins Cell Biology Dendritic Cells Bacterial Load Peptide Fragments Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal 030104 developmental biology Jaw Animal Studies TLR4 biology.protein Head |
| Zdroj: | PLoS ONE, Vol 14, Iss 1, p e0210979 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0210979 |
| Popis: | Interaction between surfactant protein-A (SP-A) and toll-like receptor (TLR)4 plays a critical role in host defense. In this work, we studied the host defense function of SPA4 peptide (amino acids GDFRYSDGTPVNYTNWYRGE), derived from the TLR4-interacting region of SP-A, against Pseudomonas aeruginosa. We determined the binding of SPA4 peptide to live bacteria, and its direct antibacterial activity against P. aeruginosa. Pro-phagocytic and anti-inflammatory effects were investigated in JAWS II dendritic cells and primary alveolar macrophages. The biological relevance of SPA4 peptide was evaluated in a mouse model of acute lung infection induced by intratracheal challenge with P. aeruginosa. Our results demonstrate that the SPA4 peptide does not interact with or kill P. aeruginosa when cultured outside the host. The SPA4 peptide treatment induces the uptake and localization of bacteria in the phagolysosomes of immune cells. At the same time, the secreted amounts of TNF-α are significantly reduced in cell-free supernatants of SPA4 peptide-treated cells. In cells overexpressing TLR4, the TLR4-induced phagocytic response is maintained, but the levels of TLR4-stimulated TNF-α are reduced. Furthermore, our results demonstrate that the therapeutic administration of SPA4 peptide reduces bacterial burden, inflammatory cytokines and chemokines, intracellular signaling, and lactate levels, and alleviates lung edema and tissue damage in P. aeruginosa-infected mice. Together, our results suggest that the treatment with SPA4 peptide can help control the bacterial burden, inflammation, and tissue injury in a P. aeruginosa lung infection model. |
| Databáze: | OpenAIRE |
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