Viral Immunity and Immunopathology
Research Group Head
Associate Professor Michelle Tate and her team are investigating the mechanisms involved in the induction and regulation of inflammation during severe and fatal viral infections including influenza. This expert knowledge will be used to develop life-saving therapies.
One focus is the influenza A virus, the virus responsible for the ‘flu’. There is a continual threat that novel influenza viruses will emerge in humans with devastating consequences for global health and the economy. Highly pathogenic influenza viruses currently circulate in wild birds and sporadic infections of humans do occur with high mortality rates of 40-60 per cent. Experts predict a future ‘bird flu’ pandemic is inevitable and without effective drugs we are currently ill-prepared.
Your immune system plays a critical role in limiting and resolving viral infections. However, excessive inflammation elicited during severe viral infections leads to the development of life-threatening disease. Patients often present to hospital with severe disease, several days after the onset of symptoms. There are currently no effective or targeted drugs or therapies in use to limit immunopathology and disease at this stage of the infection.
Utilising a range of preclinical models and techniques, influenza expert Associate Professor Tate and her team aim to gain a greater understanding of the mechanisms involved in the induction and regulation of a hyperinflammatory response and identify novel therapeutic targets and treatment strategies that limit hyperinflammation. Critically, through strong and productive collaborations with industry we endeavour to bring our discoveries to the clinic.
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.
Tate MD, Job ER, Deng YM, Gunalan V, Maurer-Stroh S, Reading PC (2014) Playing hide and seek: how glycosylation of the influenza virus hemagglutinin can modulate the immune response to infection. Viruses 6:1294-1316.
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, Job ER, Brooks AG, Reading PC (2011) Glycosylation of the hemagglutinin modulates the sensitivity of H3N2 influenza viruses to innate proteins in airway secretions and virulence in mice. Virology 413:84-92.
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.