Pattern Recognition Receptors and Inflammation Research Group
Research Group Head
Within the innate immune system, there are mechanisms to recognise and respond to both foreign and self-danger signals. These signals may be bacterial or viral infections or dead/ stressed cells in the host. These responses form the basis of our immune system.
Toll-like receptors (TLRs) constitute a group of three pattern recognition receptors (PRRs) superfamilies, NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). TLRs are implicated not only in infectious diseases, but also a broad range of chronic inflammatory and autoimmune diseases such as atherosclerosis, asthma, lupus, diabetes, arthritis and cancer.
A/Prof Mansell and his team are interested in three main research themes related to the TLR superfamily of receptors.
- PRRs signal transduction and the pro-inflammatory response
- The inflammasome in pathogenic and inflammatory disease
- The inflammasome in innate immunity
The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4. Verstak B, Stack J, Ve T, Mangan M, Hjerrild K, Jeon J, Stahl R, Latz E, Gay N, Kobe B, Bowie AG, Mansell A. J Leukoc Biol. 2014 Sep;96(3):427-36. doi: 10.1189/jlb.2A0913-487R. Epub 2014 May 8.
Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation. Dowling JK, Becker CE, Bourke NM, Corr SC, Connolly DJ, Quinn SR, Pandolfi PP, Mansell A, O’Neill LA. J Biol Chem. 2014 Mar 7;289(10):6429-37. doi: 10.1074/jbc.M113.539692. Epub 2014 Jan 9
Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. McAuley JL, Tate MD, MacKenzie-Kludas CJ, Pinar A, Zeng W, Stutz A, Latz E, Brown LE, Mansell A. PLoS Pathog. 2013;9(5):e1003392. doi: 10.1371/journal.ppat.1003392. Epub 2013 May 30.
The hepatitis B e antigen (HBeAg) targets and suppresses activation of the toll-like receptor signaling pathway. Lang T, Lo C, Skinner N, Locarnini S, Visvanathan K, Mansell A. J Hepatol. 2011 Oct;55(4):762-9. doi: 10.1016/j.jhep.2010.12.042. Epub 2011 Feb 18.
MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses. Verstak B, Nagpal K, Bottomley SP, Golenbock DT, Hertzog PJ, Mansell A. J Biol Chem. 2009 Sep 4;284(36):24192-203. doi: 10.1074/jbc.M109.023044. Epub 2009 Jul 10.
Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Mansell A, Smith R, Doyle SL, Gray P, Fenner JE, Crack PJ, Nicholson SE, Hilton DJ, O’Neill LA, Hertzog PJ. Nat Immunol. 2006 Feb;7(2):148-55. Epub 2006 Jan 15. STAT1 plays a role in TLR signal transduction and inflammatory responses. Luu K, Greenhill CJ, Majoros A, Decker T, Jenkins BJ, Mansell A Immunol Cell Biol, 2014, In Press
The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4.Verstak B, Stack J, Ve T, Mangan M, Hjerrild K, Jeon J, Stahl R, Latz E, Gay N, Kobe B, Bowie AG, Mansell A. J Leukoc Biol. 2014 May 8. pii: jlb.2A0913-487R. [Epub ahead of print]
Promyelocytic Leukemia Protein Interacts with the Apoptosis-associated Speck-like Protein to Limit Inflammasome Activation. Dowling JK, Becker CE, Bourke NM, Corr SC, Connolly DJ, Quinn SR, Pandolfi PP, Mansell A*, O’Neill LA*.J Biol Chem. 2014 Mar 7;289(10):6429-37
Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. McAuley JL, Tate MD, MacKenzie-Kludas CJ, Pinar A, Zeng W, Stutz A, Latz E, Brown LE, Mansell A. PLoS Pathog. 2013;9(5):e1003392.
A type III effector antagonizes death receptor signalling during bacterial gut infection. Pearson JS, Giogha C, Ong SY, Kennedy CL, Kelly M, Robinson KS, Lung TW, Mansell A, Riedmaier P, Oates CV, Zaid A, Mühlen S, Crepin VF, Marches O, Ang CS, Williamson NA, O’Reilly LA, Bankovacki A, Nachbur U, Infusini G, Webb AI, Silke J, Strasser A, Frankel G, Hartland EL. Nature. 2013 Sep 12;501(7466):247-51