PMID- 27996041
OWN - NLM
STAT- MEDLINE
DCOM- 20180713
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Dec 20
TI  - Leptospira surface adhesin (Lsa21) induces Toll like receptor 2 and 4 mediated 
      inflammatory responses in macrophages.
PG  - 39530
LID - 10.1038/srep39530 [doi]
LID - 39530
AB  - 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-kappaB. 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.
FAU - Faisal, Syed M
AU  - Faisal SM
AD  - National Institute of Animal Biotechnology, Hyderabad, India.
FAU - Varma, Vivek P
AU  - Varma VP
AD  - National Institute of Animal Biotechnology, Hyderabad, India.
FAU - Subathra, M
AU  - Subathra M
AD  - National Institute of Animal Biotechnology, Hyderabad, India.
FAU - Azam, Sarwar
AU  - Azam S
AD  - National Institute of Animal Biotechnology, Hyderabad, India.
FAU - Sunkara, Anil K
AU  - Sunkara AK
AD  - National Institute of Animal Biotechnology, Hyderabad, India.
FAU - Akif, Mohd
AU  - Akif M
AD  - Department of Biochemistry, School of Life Sciences, University of Hyderabad, 
      Hyderabad, India.
FAU - Baig, Mirza S
AU  - Baig MS
AD  - Centre for Biosciences and Biomedical Engineering, Indian Institute of 
      Technology, Indore, MP, India.
FAU - Chang, Yung-Fu
AU  - Chang YF
AD  - Department of Population Medicine and Diagnostic Sciences, College of Veterinary 
      Medicine, Cornell University, Ithaca, NY, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161220
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Cytokines)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adhesins, Bacterial/*immunology
MH  - Animals
MH  - Antibodies, Neutralizing/immunology
MH  - Cell Line
MH  - Cytokines/immunology
MH  - Female
MH  - HEK293 Cells
MH  - Humans
MH  - Immunity, Innate
MH  - Inflammation
MH  - Leptospira
MH  - Leptospirosis/*immunology
MH  - MAP Kinase Signaling System
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/immunology
MH  - Phosphorylation
MH  - Protein Interaction Mapping
MH  - RAW 264.7 Cells
MH  - Recombinant Proteins/immunology
MH  - Signal Transduction
MH  - Toll-Like Receptor 2/*immunology
MH  - Toll-Like Receptor 4/*immunology
PMC - PMC5172228
EDAT- 2016/12/21 06:00
MHDA- 2018/07/14 06:00
PMCR- 2016/12/20
CRDT- 2016/12/21 06:00
PHST- 2016/09/02 00:00 [received]
PHST- 2016/11/23 00:00 [accepted]
PHST- 2016/12/21 06:00 [entrez]
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2018/07/14 06:00 [medline]
PHST- 2016/12/20 00:00 [pmc-release]
AID - srep39530 [pii]
AID - 10.1038/srep39530 [doi]
PST - epublish
SO  - Sci Rep. 2016 Dec 20;6:39530. doi: 10.1038/srep39530.