A/Prof Mansell’s group uses a range of cellular and molecular biology methods, live cell microscopy, preclinical models and clinical studies to provide a molecular understanding of innate immunity.

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.

Research Group

• Callum Docherty, Research Assistant, Research Support Staff
• Hassan Albargy, PhD Student
• Kristian Barry, PhD Student

Selected publications

• Verstak B, Stack J, Ve T, Mangan M, Hjerrild K, Jeon J, Stahl R, Latz E, Gay N, Kobe B, Bowie AG, Mansell A (2014) The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4. J Leukoc Biol 96(3):427-36. doi: 10.1189/jlb.2A0913-487R. Epub 2014 May 8.

• Dowling JK, Becker CE, Bourke NM, Corr SC, Connolly DJ, Quinn SR, Pandolfi PP, Mansell A, O’Neill LA (2014) Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation.  J Biol Chem 289(10):6429-37. doi: 10.1074/jbc.M113.539692. Epub 2014 Jan 9.

• McAuley JL, Tate MD, MacKenzie-Kludas CJ, Pinar A, Zeng W, Stutz A, Latz E, Brown LE, Mansell A (2013) Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog 9(5):e1003392. doi: 10.1371/journal.ppat.1003392. Epub 2013 May 30.

• Lang T, Lo C, Skinner N, Locarnini S, Visvanathan K, Mansell A (2011) The hepatitis B e antigen (HBeAg) targets and suppresses activation of the toll-like receptor signaling pathway. J Hepatol 55(4):762-9. doi: 10.1016/j.jhep.2010.12.042. Epub 2011 Feb 18.

• Verstak B, Nagpal K, Bottomley SP, Golenbock DT, Hertzog PJ, Mansell A (2009) MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses.  J Biol Chem 284(36):24192-203. doi: 10.1074/jbc.M109.023044. Epub 2009 Jul 10.

• Mansell A, Smith R, Doyle SL, Gray P, Fenner JE, Crack PJ, Nicholson SE, Hilton DJ, O’Neill LA, Hertzog PJ (2006) Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation.  Nat Immunol (2):148-55. Epub 2006 Jan 15.

• Luu K, Greenhill CJ, Majoros A, Decker T, Jenkins BJ, Mansell A (2014) STAT1 plays a role in TLR signal transduction and inflammatory responses. Immunol Cell Biol In Press.

• Verstak B, Stack J, Ve T, Mangan M, Hjerrild K, Jeon J, Stahl R, Latz E, Gay N, Kobe B, Bowie AG, Mansell A (2014) The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4. J Leukoc Biol pii: jlb.2A0913-487R. [Epub ahead of print]

• Dowling JK, Becker CE, Bourke NM, Corr SC, Connolly DJ, Quinn SR, Pandolfi PP, Mansell A*, O’Neill LA* (2014) Promyelocytic Leukemia Protein Interacts with the Apoptosis-associated Speck-like Protein to Limit Inflammasome Activation. J Biol Chem 289(10):6429-37.

• McAuley JL, Tate MD, MacKenzie-Kludas CJ, Pinar A, Zeng W, Stutz A, Latz E, Brown LE, Mansell A (2013) Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog 9(5):e1003392.

• 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 (2013) A type III effector antagonizes death receptor signalling during bacterial gut infection.  Nature 501(7466):247-51.