Polycarpou, A;
Holland, MJ;
Karageorgiou, I;
Eddaoudi, A;
Walker, SL;
Willcocks, S;
Lockwood, DNJ;
(2016)
Mycobacterium leprae Activates Toll-Like Receptor-4 Signaling and Expression on Macrophages Depending on Previous Bacillus Calmette Guerin Vaccination.
Frontiers in Cellular and Infection Microbiology
, 6
, Article 72. 10.3389/fcimb.2016.00072.
Preview |
Text
Eddaoudi_fcimb-06-00072.pdf - Published Version Download (1MB) | Preview |
Abstract
Toll-like receptor (TLR)-1 and TLR2 have been shown to be receptors for Mycobacterium leprae (M. leprae), yet it is unclear whether M. leprae can signal through alternative TLRs. Other mycobacterial species possess ligands for TLR4 and genetic association studies in human populations suggest that people with TLR4 polymorphisms may be protected against leprosy. Using human embryonic kidney (HEK)-293 cells co-transfected with TLR4, we demonstrate that M. leprae activates TLR4. We used human macrophages to show that M. leprae stimulation of cytokine production is diminished if pre-treated with TLR4 neutralizing antibody. TLR4 protein expression was up-regulated on macrophages derived from non-bacillus Calmette-Guerin (BCG) vaccinated healthy volunteers after incubation with M. leprae, whereas it was down-regulated in macrophages derived from BCG-vaccinated donors. Finally, pre-treatment of macrophages derived from BCG-naive donors with BCG reversed the effect of M. leprae on TLR4 expression. This may be a newly described phenomenon by which BCG vaccination stimulates “non-specific” protection to the human immune system.
| Type: | Article |
|---|---|
| Title: | Mycobacterium leprae Activates Toll-Like Receptor-4 Signaling and Expression on Macrophages Depending on Previous Bacillus Calmette Guerin Vaccination |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fcimb.2016.00072 |
| Publisher version: | http://doi.org/10.3389/fcimb.2016.00072 |
| Language: | English |
| Additional information: | © 2016 Polycarpou, Holland, Karageorgiou, Eddaoudi, Walker, Willcocks and Lockwood. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, Microbiology, bacillusCalmette-Guerin, macrophages, Mycobacteriumleprae, signaling, Toll-likereceptor-4, trained immunity, leprosy, BOVIS BCG INFECTION, HUMAN MONOCYTES, TUBERCULOSIS, LEPROSY, LIPOOLIGOSACCHARIDES, TLR4, RESPONSES, TRIF, LIPOPOLYSACCHARIDE, PATHWAYS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1506351 |
Archive Staff Only
 |
View Item |
