ABSTRACT
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.
Subject(s)
Adhesins, Bacterial/immunology , Leptospirosis/immunology , Macrophages/immunology , Toll-Like Receptor 2/immunology , Toll-Like Receptor 4/immunology , Animals , Antibodies, Neutralizing/immunology , Cell Line , Cytokines/immunology , Female , HEK293 Cells , Humans , Immunity, Innate , Inflammation , Leptospira , MAP Kinase Signaling System , Mice , Mice, Inbred C57BL , Myeloid Differentiation Factor 88/immunology , Phosphorylation , Protein Interaction Mapping , RAW 264.7 Cells , Recombinant Proteins/immunology , Signal TransductionABSTRACT
Synthesis of silver nanoparticles using microorganism are many, but there are only scanty reports using actinobacteria. In the present study, the actinobacterium of the genus Sinomonas was reported to synthesis silver nanoparticles for the first time. A photo-irradiation based method was developed for the synthesis of silver nanoparticles, which includes two day old cultural supernatant of novel species Sinomonas mesophila MPKL 26 and silver nitrate solution, exposed to sunlight. The preliminary synthesis of silver nanoparticles was noted by the color change of the solution from colorless to brown; the synthesis was further confirmed using UV-visible spectroscopy which shows a peak between 400 and 450nm. Spherical shape silver nanoparticles of size range 4-50nm were synthesized, which were characterized using transmission electron microscopy. The Fourier transform infrared spectroscopy result indicates that, the metabolite produced by the novel species S. mesophila MPKL 26 was the probable reducing/capping agent involved in the synthesis of silver nanoparticles. The synthesized silver nanoparticles maintained consistent shape with respect to different time periods. The synthesized silver nanoparticles were evaluated for the antimicrobial activity against multi drug resistant Staphylococcus aureus which show good antimicrobial activity. The method developed for synthesis is easy, requires less time (20min) and produces spherical shape nanoparticles of size as small as 4nm, having good antimicrobial activity. Hence, our study enlarges the scope of actinobacteria for the rapid biosynthesis of silver nanoparticles and can be used in formulating remedies for multi drug resistant S. aureus.
Subject(s)
Anti-Bacterial Agents/pharmacology , Metal Nanoparticles/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Micrococcaceae/metabolism , Silver/chemistry , Sunlight , Microscopy, Electron, TransmissionABSTRACT
Chunni (a piece of cloth worn around the neck by many Indian women) is a well recognized accidental ligature around the neck. We report a rare case of accidental strangulation with chunni where the patient was pillion rider on bicycle; in spite of very common of use of bicycle to best our knowledge this kind of injury has not been reported previously.
Subject(s)
Accidents , Asphyxia/etiology , Bicycling , Clothing , Neck Injuries/etiology , Asphyxia/pathology , Culture , Female , Forensic Pathology , Humans , India , Neck Injuries/pathology , Unconsciousness/etiology , Vomiting/etiology , Young AdultABSTRACT
We present an illustrative case of osteoid osteoma of the femur, in an 11 year old male child where the clinical features were masquerading the diagnosis of tethered cord syndrome and lead to the delay in diagnosis.