Transcript Slide 1

About the Speaker:
Program in Emerging Infectious
Diseases (EID)
“Toll-like receptor signaling in innate
immunity: just what does MAL do”
By Dr Ashley Mansell
Monash Institute of Medical Research
Toll‐Like Receptor (TLR) Signalling Laboratory
Abstract:
Initiation of the innate immune response requires agonist
recognition by pathogen-recognition receptors such as the
Toll-like receptors (TLRs). TIR domain-containing adaptors
are critical in orchestrating the signal transduction pathways
after TLR activation and are responsible for ‘scultping’ the
optimal immune response. MAL/ TIRAP is involved in
bridging MyD88 to TLR2 and TLR4 in response to bacterial
infection. Our studies have characterised the role of MAL in
regulating the activation of innate immunity via NF-B
induction of pro-inflammation and the critical role MAL plays
in signal transduction.
We have also recently begun investigating the role of the
Influenza A virus protein PB1-F2 found in pandemic strains
of IAV and its role in inflammation. We show that PB1-F2
from pathogenic IAV induces IL-1 secretion via caspase-1
and the NLRP3 inflammasome in humans and mice.
Inflammation induced by PB1-F2 was abrogated in NLRP3
deficient mice. To our knowledge, this is the first
characterization of the mechanism of PB1-F2-mediated
NLRP3 inflammasome complex activation, providing further
understanding of PB1-F2 contribution to the enhanced
inflammatory phenotype in pathogenic influenza infections.
All are welcome
Date : 10 August 2012(Friday)
Time : 3.00 – 4.00 pm
Host : Dr Manoj N Krishnan
Program in Emerging Infectious Diseases
Venue : Duke-NUS, Amphitheatre, 2nd Floor
Dr Ashley Mansell is a senior scientist
and head of the Toll‐Like Receptor
(TLR) Signaling Laboratory in the
Centre for Innate Immunity and
Infectious Diseases, Monash Institute of
Medical Research (MIMR), Monash
University,
Australia.
Dr
Mansell
completed his PhD at Trinity College,
Dublin, Ireland. Returning to Australia
he formed a TLR research laboratory at
MIMR where he has been engaged in
studying TLR signal transduction and its
role in inflammatory diseases. Dr
Mansell’s research group is interested in
understanding and identifying novel TLR
and other Pattern Recognition Receptor
signal transduction genes that positively
and
negatively
regulate
the
proinflammatory response following
pathogen recognition. Recent studies
have focused on viral activation of the
inflammasome and RIG-like receptor
pathways. Dr Mansell’s research also
investigates the immunomodulation of
PRR signaling by pathogens such as
their research description of Hepatitis B
virus targeting of TLR signaling. Dr
Mansell has published his research in
the highest ranking journals including
Nature, Nature Immunology, PNAS, and
the Journal of Biological Chemistry. He
heads the Australian TLR research
network, TLROZ, and established the
Infection and Immunity Special Interest
Group within the Australasian Society
for Immunology.
Duke-NUS Graduate Medical School, 8 College Road, S169857. For more information, please visit our website www.duke-nus.edu.sg