When patients arrive at hospital with an out-of-control viral infection, such as influenza, there are currently limited drugs available to help. The Tate group is identifying new treatments that limit damaging inflammation and the ability of respiratory viruses to replicate in the lung.

Overview

In Australia, hospitalisations and deaths from influenza have risen over the decade – around 3500 Australians die each year and 18,000 are hospitalised.

Associate Professor Michelle Tate, and her team are investigating how inflammation turns from protector to destroyer in severe and fatal viral infection such as influenza, COVID-19 and lifelong chronic lung diseases, chronic obstructive pulmonary disease (COPD) and silicosis.

During a severe viral infection your immune system overreacts causing out-of-control inflammation that can turn fatal. Patients who experience this hyperinflammatory response usually only seek hospital treatment after several days of symptoms, by which point there are no effective targeted drugs or therapies to limit the development of the life-threatening viral infection.

By studying the steps and processes involved in the induction and regulation of a hyperinflammatory response, A/Prof Tate and her team are identifying therapeutic targets and treatment strategies to limit hyperinflammation and save lives.

“Without effective drugs to treat damaging inflammation, we will always be at risk. The threat of new viruses emerging and causing widespread devastation is always present,” said A/Prof Tate.

Areas of focus

• Tackling hyperinflammation and severe influenza
• Novel host-directed therapies for influenza
• Developing new drugs to reduce silicosis lung disease

READ A/PROF TATE’S 2023 FLU REPORT

Links

Twitter

Research Group

• Dr Christopher Harpur, Postdoctoral Scientist
• Dr Maggie Lam, Postdoctoral Scientist
• Dr Alison West, Postdoctoral Scientist
• Christopher Hodges, Research Assistant, Research Support Staff
• Sarah Rosli, PhD Student
• Kristian Barry, PhD Student

Selected publications

• Harpur CM, West AC, Le Page MA, Lam M, Hodges C, Oseghale O, Gearing AJ, Tate MD (2023) Naturally derived cytokine peptides limit virus replication and severe disease during influenza A virus infection. Clin Transl Immunology. 12:e1443.

• Coldbeck-Shackley RC, Romeo O, Rosli S, Gearing LJ, Gould JA, Lim SS, Van der Hoek KH, Eyre NS, Shue B, Robertson SA, Best SM, Tate MD, Hertzog PJ, Beard MR (2023) Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection. PLoS Pathog. 19:e1010843.

• Lam M, Mansell A, Tate MD (2022) Another One Fights the Dust: Targeting the NLRP3 Inflammasome for the Treatment of Silicosis. Am J Respir Cell Mol Biol. 66:601-611.

• Bawazeer AO, Rosli S, Harpur CM, Docherty CA, Mansell A, Tate MD (2021) Interleukin-1β exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection. Immunol Cell Biol. 99:737-748.

• Laghlali G, Lawlor KE, Tate MD (2020) Die Another Way: Interplay between Influenza A Virus, Inflammation and Cell Death. Viruses. 12(4).

• Rosli S, Kirby FJ, Lawlor KE, Rainczuk K, Drummond GR, Mansell A, Tate MD (2019) Repurposing drugs targeting the P2X7 receptor to limit hyperinflammation and disease during influenza virus infection. British J Pharm. 176(19):3834-3844.

• Tate MD, Ong JD, Dowling JK, McAuley JL, Robertson AB, Latz E, Drummond GR, Cooper MA, Hertzog PJ, Mansell A (2016) Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition. Sci Rep 6:27912.

• Thomas BJ, Porritt RA, Hertzog PJ, Bardin PG, Tate MD (2014) Glucocorticosteroids enhance replication of respiratory viruses: effect of adjuvant interferon. Sci Rep 4:7176.

• 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:e1003392.

• Tate MD, Brooks AG, Reading PC, Mintern JD (2012) Neutrophils sustain effective CD8⁺ T-cell responses in the respiratory tract following influenza infection. Immunol Cell Biol 90:197-205.

• Tate MD, Brooks AG, Reading PC (2011) Specific sites of N-linked glycosylation on the hemagglutinin of H1N1 subtype influenza A virus determine sensitivity to inhibitors of the innate immune system and virulence in mice. J Immunol 187:1884-1894.

• Tate MD, Ioannidis LJ, Croker B, Brown LE, Brooks AG, Reading PC (2011) The role of neutrophils during mild and severe influenza virus infections of mice. PLoS One 6:e17618.

• Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC (2010) Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J Virol 84:7569-7580.

• Tate MD, Deng YM, Jones JE, Anderson GP, Brooks AG, Reading PC (2009) Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol 183:7441-7450.