Leptospira surface adhesin (Lsa21) induces Toll like receptor 2 and 4 mediated inflammatory responses in macrophages
| Autor: | Syed M. Faisal, M. Subathra, Vivek Phani Varma, Anil K. Sunkara, Yung-Fu Chang, Mohd Akif, Sarwar Azam, Mirza S. Baig |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAP Kinase Signaling System 030106 microbiology Article Cell Line Proinflammatory cytokine Mice 03 medical and health sciences Leptospira Protein Interaction Mapping Animals Humans Leptospirosis Phosphorylation Adhesins Bacterial Inflammation Toll-like receptor Multidisciplinary Innate immune system biology Chemistry Macrophages biology.organism_classification Antibodies Neutralizing Immunity Innate Recombinant Proteins Toll-Like Receptor 2 Cell biology Mice Inbred C57BL Toll-Like Receptor 4 TLR2 HEK293 Cells RAW 264.7 Cells 030104 developmental biology Myeloid Differentiation Factor 88 Immunology TLR4 Cytokines bacteria Female Cytokine secretion Signal transduction Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep39530 |
| Popis: | Leptospirosis is zoonotic and emerging infectious disease of global importance. Little is understood about Leptospira pathogenesis and host immune response. In the present work we have investigated how Leptospira modulates the host innate immune response mediated by Toll-like receptors (TLRs) via surface exposed proteins. We screened Leptospira outer membrane/surface proteins for their ability to activate/inhibit TLR2/4 signaling in HEK293 cell lines. Of these the 21 kDa Leptospira surface adhesin, Lsa21 had strong TLR2 and TLR4 activity leading to production of proinflammatory cytokines and expression of costimulatory molecules in mouse macrophages. This activity of Lsa21 on innate response was dependent on activation of mitogen activated protein kinases (MAPKs) via stimulating the rapid phosphorylation of p38, JNK and activation of transcription factor NF-κB. Additionally, neutralizing antibodies against TLR2 and TLR4 significantly inhibited cytokine secretion and attenuated Lsa21 induced phosphorylation of p38 and JNK. Furthermore, Lsa21 induced cytokine levels were significantly lower in TLR2−/− and TLR4−/− than in wild type mouse macrophage cell lines. Confocal microscopy and molecular docking confirmed that Lsa21 interacted with both TLR2 and TLR4. These results indicate that Lsa21 is a potent TLR2 and TLR4 agonist that induces strong innate response and may play important role in Leptospira pathogenesis. |
| Databáze: | OpenAIRE |
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